Friday, August 2, 2013

Purr Kitty Purr

Our cat, whizzer, is on my lap now.  He is black.  I was trying to come up with a new post and failing to come up with anything.  I have seen the cat, lion, leopard, tiger, panther depicted as guardians of heavens gate in old mythological writings.  They are such unique creations of the creator.  Each one has its own personality, yet all felines have common traits, like purring.  So as my cat settled on my lap as if he knew I needed some help with this post, I gave in to his help.  Many years ago,1991, in Maui at a pointholding seminar, I had a powerful dream with a male lion in it that still influences my path today.  The lion was laying down and had a brilliant starburst at its naval and the feeling I got from it was that it reflected the Lamb and Lion consciousness when the cats and dogs would stop warring with each other.  Peace on earth, world peace etc.. Since the animals, birds, and fishes  hold the keys to the end of time(see Revelations in the bible),  this dream set my course to study the animals and their nature.  I have worked and lived in rural/farm settings which has given me access to the basic nature of the animals.  As I observed their connection to people, it started to become clear to me that they are here to teach us one basic tenant of the creator, ie no sex during pregnancy.  The reason they are given the responsibility to end time is that Man has throughout the ages disobeyed this one tenant of the creator and is obviously going to continue making time his master and keep fucking up his kids the way he was fucked up.  Wow, how can I mix such vulgar language while speaking of the creator?  Well, none of us got here without someone fucking someone.  Get over it.  Sex rules the world of humans and animals.  The creator programmed the DNA of the animals not to have sex after conception as an example of how humans should govern their sexual energy.  When we don’t, the collective anger suppressed in the fetal consciousness manifests as war and self destruction, something the world seems hell bent on fulfilling as we are condemned to repeat that which we can’t remember.  ”History repeats itself”.   The creator has tried for eons to allow humanity to figure out the connection to this pattern and in this cycle has given us such wonderful tools to view the fetal experience.  These tools could be used to end the debate I am raising again.  I have found research done in the 70′s monitoring the fetal heart rate during maternal orgasm and it was labeled as  ”ominous”, but the current technology is so much more advanced that we could figure this out on our own and stop the cyclical pattern of destroying ourselves.  The free will humans enjoy has consequences of self destruction when we ignore the creators laws of life.  Death, dying and destruction are the rewards we reap.  As I read the OAHSPE Bible and realize the commandment “Thou shalt not commit adultery” really means don’t lay with your wife during pregnancy and that this commandment is the first target of the false gods and dark angels to inspire man to disobey as makes room for our clouded vision, unable to hear the creators voice, allows the unlimited “entities” to inhabit our fleshly temple and take us to the grave believing in a savior to save us from our pain and sins.  This same pattern of Saviorism has been repeated on this planet so many times.  Saint Germaine states in the I AM discourses that 95% of aging and death is due to misuse of the sexual energy.  Ascended masters, physically immortal,  have mastered their sexual energy and are androgenous, which means equally male and female, yin and yang.  The pain/pleasure complex imposed on the fetus during maternal orgasm is so real.  This fetal language is expressed in all our love songs.  Its as plain as the nose on our face.  When two people are sexually intimate, their navals touch, the record of their individual fetal experience is awakened and shared.  They either stay together through the pain and pleasure, or they separate.  Separation on the planet keeps us from oneness.  So, to all my immortal friends in Scottsdale that read this post,  what part of what I am sharing conflicts with all that you have awakened within yourself the past 50 years of spreading the good news of physical immortality with those that are waking up to life.  The genetics of our ancestors is conquerable by sticking together through the pain and pleasure of life.  I feel a new way of looking at all the gut felt expressions that come out of our flesh can be expressed as the pain/pleasure complex.  By understanding that we have done to our children that which was done to us, ie sex during pregnancy, and that his one act is the key to our death or our physical immortality.  We have the power within us conquer our genetics with love and forgiveness.  No Savior is needed, its called Save your own ass.

One of my many teachers was John Ray who developed Body Electronics.  The Law of conquering mortality as shown to him is stated as follows, “Until man can experience on the mental level that which exists on the physical, he will be bound to the physical.”  As you are aware, I have failed in my desire to have my family follow me into Physical Immortality, yet I feel my immortality must include my prenatal memories when I was still connected to my cord and placenta, my other half.  The feeling of closeness in the womb to our mother never leaves our subconscious and we seek to find that feeling in life.  I have combined so many ideas to come up with my simple way of remembering my prenatal memories and I would love to show you how to go there yourselves.  Hence, my recent trip to Scottsdale.   I sometimes feel my desire to have others remember as I have is an exercise in futility.  If so, I continue to awaken myself and feel that as I open and conquer the genetics in me,  you automatically get it as there is only one of us.  To do this work for you, I have created this little piece of heaven here.  It isn’t much and I feel I am building it for all of us even though at this point, I am unacknowledged in my efforts and sometimes it gets hard to be motivated.  I really enjoyed just breathing with you all the little time we had together.  I will stay in touch with you.  I like the fuze meetings etc.  It would be so nice to have a few of you visit us here and help us vision a healing haven for all the immortals.  Many of you remember I gave my all in Scottsdale at bioforce for such a place.  Way ahead of my time, even now.. Dr. Paul (Billibob) is still going at his farm and I still feel him as part of me.  He has completed his book, 2 volumes, and if by chance you would like to read them, send 100.00 to PO Box 0007, Mapleton, KS and he will mail it to you direct.  No other method of purchase is available.

Well, all for now, I AM,,,, Jeff

Posted by Jeff Schofield DC in 07:14:31 | Permalink | Comments Off

Thursday, June 27, 2013

Fetal Imprinting of Parents Voice’s

It’s been a while since my last post…Since I no longer get comments on my posts, I have no way to get your feedback.  I hope my readers are still sharing my blog and please do support my online e-book available on amazon Kindle titled “Let the Fetus have its say”.

I have been driving a semi for the last ten months for transport america, a small but talented company out of Eagan, MN.. I have seen a lot of the Eastern parts of the USA which I had never been to.  I recently turned in my truck to try and grow a garden.  Seeing firsthand how helpless people in the cities are if the food isn’t on the shelf at the store, plus just wearing out with all the “crazy” drivers on the road that have no clue as to how hard it is to control a big rig, I am taking a break to heal, relax and do long overdue projects around the farm here in Richwoods, MO.  One thing I did my last 2 weeks out was to listen to the voice tapes my parents made several years back where they read their personal history onto cassette tapes as a gift to me and my siblings..   I was overwhelmed by how powerful and deep these voices I listened to in the womb for 9 months influenced my internal healing journey at a level I hadn’t experienced in the last 17 years of digging in my prenatal memories as recorded in the other posts on my blog.. So..

The vibration of their voices was imprinted into my subconscious in the womb.  No big surprise from an intellectual view in light of all the research done in recent years on pre and peinatal psychology.  These where the voices which I heard during my suffocations caused over the 9 months and multiple orgasms which I have mentioned and detailed in prior posts.  I have been experimenting with combining listening to their voices seperately and together using two tape recorders.  The latest computors have voice recognition capablilities which validate my observation that each persons voice is completely unique.

So, I use the voices of my parents to stir the fetal memories of suffocation while watching porn on my computor.  The visual with the parental audio feels so spot on in accessing the memories I have been digging in for the past 18 years.  As I watch the pornographic films, I place my consciousness inside the belly of the women in the various scenes and it has been helping me to see why I hated my parents so much.  They were just doing to me what was done to them which supports the death/dying consciousness on our “mother fucking planet”  … So my goal is to love and forgive these memories as they surface and hopefully come closer to my creator which lives in my heart.

The False Gods of the worlds major religions which took out the commandment to not have sex during pregnancy from the bible and other religious texts are the real enemy in this war for the souls of men.  In my upbringing as a “Mormon”  The false god PEI as mentioned in the OAHSPE never told Joseph Smith the whole truth about sex during pregnancy and I hold Pei accountable as he Piggy backed off the efforts of the early christians fabricated story of Jesus as the “Savior” of men.  Pei set himself up as the true Jesus and the only true church on the face of the earth in which he was pleased.  The mormon temple ceremony has the line PEI LAY AIL which means “oh god, hear the words of my mouth”, so even here in the sacred covenants of the temple, PEI revealed his true name disguised in another language.  The level of deception by these false gods is beyond belief and angers my soul to no end.  Their lies have robbed me of the respect of my own children, siblings and extended family who are so deeply immersed in the Mormon faith that they feel justified in excluding me as a member, have no contact with me due to the lies of this false god Pei and his ethereal heavens and legions of angels that spread the mormon faith throughout the world.  Each of the false gods of the earths major religions have legions of angels which inspire men to believe in them so the rule that whoever you believe in when you die is the ethereal heaven you are taken to by that false gods death angels.

The OAHSPE bible makes clear the eternal war against Jehovih, or the one creator.  The many false gods are given their day to deceive us earthlings by the power of Jehovih which gives them breath and life, but even these false gods, in order to advance beyond their false godhood, must reveal the truth to all their followers regarding Jehovih before they can advance to higher levels of understanding of the one creator.. This cycle has repeated itself countless times on this mothership earth and is all part the one creators plan for his children here on earth.

In the eye of the one creator, their is no conflict between Science and Religion. Humans create the duality by having sex during pregnancy and splitting the fetal soul between the voice of the mom and dad.  Androgeny is the return to the true voice of the one creator in us all and the ousting of the duality of the parental voices imposed during maternal orgasm.  The I AM Religious activity out of Shaumburg, IL gives a clear understanding of the I AM as the only presense acting in all creation.  The false gods know that sex during pregnancy clouds the souls memory of the true creator by imposing the pain/pleasure complex in the fleshly temples.  So the war starts by getting us earthlings to have sex during pregnancy and the impossible to overcome nature of the Pain/Pleasure complex creates an opening to have a Savior take on this pain in the story of the crucifixtion and Gethsemene,  ..The level of deception is beyond belief.  I wouldn’t believe what I am typing if I wasn’t seeing through this cloud of deception which my parents handed to me in their gernepool.  The whole idea of Family is “Fucking Torture”,,, which is the title of one of my former posts.

So, to the end of the lie that sex during pregnancy is safe I again send this message into the ethereal web of the intranet in hopes that it will set another soul free from the cloud.  I am , in love and light,  Jeffory H. Schofield  DC

Posted by Jeff Schofield DC in 02:22:08 | Permalink | Comments (3)

Saturday, November 17, 2012

Take this “TEST OF TIME”

So, here we are nearing the supposed “end of time” ,, so in order to prepare yourself for this experience, I have prepared this little quiz, yes a test, concerning what time is.  If its going to end, just might be good to understand if your ready.  So here goes, my little “TEST OF TIME”.

#1     What is time?   a)  that which runs my life?  b)  the most controlled entity on the planet?  c) both a & b

# 2    Humans have created many time pieces.  What is the most common shape of a time piece?  a) square  b) oval c) round d) rectangular

# 3    When do most humans start counting time?  a) at birth  b) at conception c) 40 days d) 45 days

#4     What is the average number of years of childhood after birth that has been forgotten?  a) 1-2  b)2-3  c)3-4  d)4-5

#5     What is the most common sound associated with time?  a) tick-tock    b)  ding-dong  c) boom-boom  d)  ping-pong

#6      What was the shape of the placenta while you were in your mothers womb?   a} square  b) oval  c) round  d) rectangular

#7     What was the most consistent sound you experienced in the womb?  a) mom breathing  b) mom’s heart beat  c) dad snoring  d)mom pissing

#8      Which time piece most closely resembles the shape of the cord & placenta?  a) grandfather clock b) wristwatch c) pocketwatch d) wall clock

#9      Time is money. So, blood money refers to which blood cell type?  a) rbc’s  b) wbc’s  c)  stem cells  d) all 3 (pennies, nickles, dimes, quarters)

#10    The cord and placenta do what?    a) run our life for 9 months  b) controls the fetal entity in its inner world  c) both a & b

So, did you pass?  As the administrator of this test, I guess I get to decide if you passed or not.  If you reached the conclusion that time is nothing more or less than all that has been forgotten by the masses of humanity regarding their earthly journey from conception to age 3 or 4, then you  passed.  Extra credit is awarded if you already understood this concept and are actively engaged in remembering all you have forgotten as this is obviously what will bring the end of time to pass.  No big mystery.  In love and light, I AM  Jeffory H. Schofield DC

Posted by Jeff Schofield DC in 17:04:26 | Permalink | Comments (1) »

Friday, August 10, 2012

MTHFR & SEX DURING PREGNANCY

Well, I am out of my league as far as this MTHFR stuff goes.  My friend Jo, the one who always challenges my theories,  is big into this MTHFR as the cause of so many illnesses that exist.  I was looking at some of the published studies she has downloaded from the web about this MTHFR and was surprised to see the scientists saying it causes developmental problems during pregnancy.  ie neural tube defects to name just one.   That got me wondering if Jo, in her very scientific approach to life was being guided by the same creator I am being guided by to come to the same conclusions on the effect of sex during pregnancy.  If so, maybe there is a study done which looked at MTHFR in relation to pre-eclampsia,  hypoxia or anoxia which I have stated for years occurs post orgasm to the fetus.  So I googled MTHFR and anoxia, and got several recently published studies supporting the link between hypoxia and MTHFR.  Likewise, Pre-eclampsia is linked to fetal hypoxia.   The history of MTHFR stems from mapping the human genome,,,,it was rather anticlimactic as humans and worms are about the same.. So, current research is looking at epigenetic factors which influence the genetic code.  Epigenetics is the study of the environment during development with conception to age 3-4 having the most dominant effects.  The big mystery to me is that they don’t talk about the common human experience of maternal orgasm in their seeking for answers anymore.  After the rude realization of researchers in the 70′s & 80″s that maternal orgasm causes anoxia, hypoxia, bradychardia and increased fetal movemnet, the research was shut down.  Shame won the day.. But now, this MTHFR business is bringing the same conclusions as then, yet there is no one willing to stick their neck out and condemn sex during pregnancy, EXCEPT ME AND OTHERS I HOPE TO MEET,..  The researchers still tuck their tails and say they don’t know why MTHFR is there.  The old saying, “Resistance obscures awarenes” comes to mind as these well funded researchers steer the results and conclusions away from the bedroom where they themselves once faced the one eyed snake.  I keep challenging them to wake up and maybe it is happening as the light within them guides them gently to the conclusions of oneness which we all experienced in the womb.  This must necessarily come from within their own consciousness or else it is simply imposed and the old saying “One convinced against his will, is of the same opinion still”, gets another chance to manifest.  The link below is the full text article link  I mentioned above.  I am also going to see if I can imbed the whole article for your convenience.

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0016681

Epistasis between COMT and MTHFR in Maternal-Fetal
Dyads Increases Risk for Preeclampsia
Lori D. Hill1, Timothy P. York2,3, Juan P. Kusanovic4,5,6, Ricardo Gomez5,6, Lindon J. Eaves2,3, Roberto
Romero4, Jerome F. Strauss, III1*
1 Department of Obstetrics and Gynecology, Virginia Commonwealth University School of Medicine, Richmond, Virginia, United States of America, 2 Virginia Institute for
Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, Richmond, Virginia, United States of America, 3 Department of Human and
Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, Virginia, United States of America, 4 Perinatology Research Branch, National
Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, and Detroit, Michigan,
United States of America, 5 Department of Obstetrics and Gynecology, So´ tero del Rı´o Hospital, Santiago, Chile, 6 Department of Obstetrics and Gynecology, Pontificia
Universidad Cato´ lica de Chile, Santiago, Chile
Abstract
Preeclampsia is a leading cause of perinatal morbidity and mortality. This disorder is thought to be multifactorial in origin,
with multiple genes, environmental and social factors, contributing to disease. One proposed mechanism is placental
hypoxia-driven imbalances in angiogenic and anti-angiogenic factors, causing endothelial cell dysfunction. Catechol-Omethyltransferase
(Comt)-deficient pregnant mice have a preeclampsia phenotype that is reversed by exogenous 2-
methoxyestradiol (2-ME), an estrogen metabolite generated by COMT. 2-ME inhibits Hypoxia Inducible Factor 1a, a
transcription factor mediating hypoxic responses. COMT has been shown to interact with methylenetetrahydrofolate
reductase (MTHFR), which modulates the availability of S-adenosylmethionine (SAM), a COMT cofactor. Variations in MTHFR
have been associated with preeclampsia. By accounting for allelic variation in both genes, the role of COMT has been
clarified. COMT allelic variation is linked to enzyme activity and four single nucleotide polymorphisms (SNPs) (rs6269, rs4633,
rs4680, and rs4818) form haplotypes that characterize COMT activity. We tested for association between COMT haplotypes
and the MTHFR 677 CRT polymorphism and preeclampsia risk in 1103 Chilean maternal-fetal dyads. The maternal ACCG
COMT haplotype was associated with reduced risk for preeclampsia (P = 0.004), and that risk increased linearly from low to
high activity haplotypes (P = 0.003). In fetal samples, we found that the fetal ATCA COMT haplotype and the fetal MTHFR
minor ‘‘T’’ allele interact to increase preeclampsia risk (p = 0.022). We found a higher than expected number of patients with
preeclampsia with both the fetal risk alleles alone (P = 0.052) and the fetal risk alleles in combination with a maternal
balancing allele (P,0.001). This non-random distribution was not observed in controls (P = 0.341 and P = 0.219, respectively).
Our findings demonstrate a role for both maternal and fetal COMT in preeclampsia and highlight the importance of
including allelic variation in MTHFR.
Citation: Hill LD, York TP, Kusanovic JP, Gomez R, Eaves LJ, et al. (2011) Epistasis between COMT and MTHFR in Maternal-Fetal Dyads Increases Risk for
Preeclampsia. PLoS ONE 6(1): e16681. doi:10.1371/journal.pone.0016681
Editor: Hongmei Wang, Institute of Zoology, Chinese Academy of Sciences, China
Received October 11, 2010; Accepted December 22, 2010; Published January 31, 2011
This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public
domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
Funding: This research was supported in part by grants from the NCMHD P60 MD002256 (JFS) and the Perinatology Research Branch, Division of Intramural
Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS, N01 HD-2-3342 (JFS). The funders had no role in study
design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
* E-mail: jfstrauss@vcu.edu
Introduction
Preeclampsia (PE) affects 5–8% of pregnancies worldwide and is
characterized by hypertension and proteinuria after 20 weeks of
gestation[1]. Although preeclampsia remains a significant source
of maternal and perinatal mortality and morbidity, its etiology
remains unclear. A genetic susceptibility to preeclampsia has been
well established and genes involved with endothelial dysfunction,
oxidative stress, angiogenesis and thrombophilia have been
associated with preeclampsia[2–5].
It has long been recognized that preeclampsia is a placental
disorder that results in the maternal syndrome. Placental hypoxia
is a key feature of this condition and placentas from patients with
preeclampsia show shallow trophoblast invasion[6–8] and failure
of vascular transformation of the spiral arteries[9–11]. During
normal placentation, oxygen levels tightly control the balance
between angiogenic and anti-angiogenic factors to ensure
adequate remodeling of the maternal spiral arteries and sufficient
placental blood supply[12]. It is postulated that a hypoxia-driven
disruption of the angiogenic balance causes the placenta to
release factors that lead to intravascular inflammation[13–15],
endothelial dysfunction[16–20] and the maternal phenotype.
Indeed, abnormal concentrations of circulating angiogenic and
anti-angiogenic factors including soluble fms-like tyrosine kinase
(sFlt1), placental growth factor (PlGF), vascular endothelial growth
factor (VEGF), transforming growth factor beta (TGF-b), and
soluble endoglin (sENG) have been well documented in preeclampsia[
12,18,19,21–25]. Although abnormalities in these
factors have been consistently demonstrated, there is no discernable
pattern that characterizes preeclampsia, suggesting that a
defect in an upstream regulator may contribute to the pathophysiology
of preeclampsia.
PLoS ONE | www.plosone.org 1 January 2011 | Volume 6 | Issue 1 | e16681
2-methoxyestradiol (2-ME) is a natural metabolite of estradiol
and it is generated by catechol-O-methyltransferase (COMT) in
the placenta. 2-ME is a compound with diverse biological activities
including inhibition of Hypoxia Inducible Factor 1a (HIF-
1a)[26,27]. HIF-1a is a transcription factor that mediates cellular
responses to hypoxia and its expression is altered in preeclampsia[
26–28]. Cytotrophoblastic invasion has also recently been
reported to be modulated by 2-ME during hypoxic conditions[29].
In collaboration with Kanasaki et al., we found that the Comtdeficient
pregnant mouse exhibits a preeclampsia phenotype
similar to that found in human preeclampsia, including hypertension,
proteinuria and vascular and placental lesions; and the mouse
preeclampsia-like phenotype is reversed by administration of 2-
ME[27]. In this same report, circulating concentrations of 2-ME
and placental COMT activity were significantly reduced in
women diagnosed with preeclampsia, raising the possibility that
altered production of 2-ME may contribute to the pathophysiology
of preeclampsia by altering the placental response to
hypoxia[27]. Moreover, severe preeclampsia and fetal growth
restriction have been associated with reduced placental COMT
activity[30,31]. HIF-1a is an upstream regulator of many of the
factors implicated in the angiogenic balance and endothelial
dysfunction[12,28]. By modulating HIF-1a activity, COMT
represents a point at which this upstream regulator could be
disrupted.
Human allelic variation in COMT has been associated with
changes in enzyme activity levels[32,33]. COMT is one of several
enzymes that degrades catecholamines and is involved in vascular
and metabolic homeostasis, including dopamine, epinephrine,
norepinephrine, and catechol estrogens. The COMT enzyme is
involved in a wide variety of physiological processes, such as
prefrontal cortex function and lipid metabolism, and has been
implicated in diseases such as schizophrenia, pain sensitivity,
Parkinson’s disease, and cancer[33–37]. Previous studies investigating
the role of genetic variation in COMT have largely focused
on the single nucleotide polymorphism (SNP) rs4680 Val158Met,
which has been associated with a modest 4-fold difference in
activity[32]. However, a recent functional analysis of four SNPs,
rs6269, rs4633, rs4818, and rs4680, demonstrated that enzymatic
activity is more precisely determined by three haplotypes of these
SNPs, which result in a 25-fold difference in enzyme activity[33].
Preeclampsia is thought to be multifactorial in origin with
multiple genes, environmental, and social factors acting in
conjunction to cause disease[38–40]. Variations in the methylenetetrahydrofolate
reductase (MTHFR) gene have been associated
with elevated homocysteine, a risk factor for endothelial
dysfunction, vascular disease, and preeclampsia[41–44]. Some
previous studies have shown allelic variations in MTHFR to be
associated with preeclampsia, although others have failed to
replicate these associations[4,45,46]. MTHFR modulates the
availability of methyl groups[44], which are the cosubstrate for
COMT[32] and Roffman et al. recently showed that stratifying
COMT genotypes by MTHFR genotype revealed a role of COMT
in prefrontal cortex function[32,44,47].
In the present case-control study, we investigated the association
between COMT haplotypes and preeclampsia in 1,103 Chilean
maternal-fetal dyads. Haplotype frequencies were determined by
genotyping 4 SNPs from the COMT gene: rs6269, rs4633, rs4818,
and rs4680. Based on previous findings of haplotype-specific
differences in enzymatic activity and protein levels, we evaluated
the relationship of the functional variation linked to COMT
haplotype and preeclampsia[33]. Finally, we assessed whether the
relationship between COMT and preeclampsia was influenced by
MTHFR.
Results
Table 1 displays the demographic and clinical characteristics of
mothers and neonates from pregnancies with preeclampsia as well
as controls. No significant differences were observed in maternal
age or neonatal sex between groups. Consistent with previous
epidemiologic studies, patients with preeclampsia showed a
significantly higher body mass index (BMI, P,0.001) and fewer
previous live births (P =0.007). In accordance with preeclampsia
resulting in intrauterine growth restriction and indicated preterm
birth, offspring born to women with preeclampsia showed a
significantly lower gestational age at delivery and birthweight
(P,0.001).
Single SNP analysis revealed no associations between COMT
polymorphisms rs6269, rs4633, rs4818, and rs4680 and preeclampsia
in either maternal or fetal samples (Table S1). All SNPs
were found to be in Hardy-Weinberg equilibrium in the maternal
and fetal control samples separately. However, haplotype analysis
showed the four SNPs to be in very high linkage disequilibrium
(LD) for both maternal and fetal samples (Table S2). Three main
haplotypes were identified: ACCG, ATCA, and GCGG (SNP
order: rs6269, rs4633, rs4818, rs4680) and correspond to the low,
intermediate, and high enzyme activities of COMT, respectively,
identified by Nackley and colleagues[33].
The haplotype analysis of COMT frequency differences between
cases and control subjects is shown in Table 2. A global test of
differences among haplotypes reached statistical significance for
maternal samples, but not for fetal samples (P = 0.016 and
P = 0.116 respectively). Separate tests for haplotype-specific effects
on disease class resulted in significant results for both the maternal
(P = 0.004) and fetal (P =0.038) ACCG haplotype (Table 2). This
haplotype was observed more frequently in controls than cases for
both maternal and fetal samples, indicating a possible protective
effect. To control for the correlation of genotypes inherent in
maternal-fetal dyads, we conditioned the maternal ACCG
haplotype by the respective fetal ACCG haplotype. This resulted
in only a significant effect of the maternal ACCG haplotype
(maternal P = 0.041; fetal P = 0.446) on risk for disease and
indicated that the effect of the ACCG haplotype was maternally
derived and initial significant result for the fetal ACCG haplotype
was likely a result of the correlation of the fetal-maternal genotype.
Additional multiple logistic regression analysis was performed to
include risk factors for preeclampsia (maternal age, BMI, and
previous live births). Results of a final regression model, which
only included covariates, found to be significant in this population
is shown in Table 3. Only the maternal ACCG haplotype
Table 1. Maternal and fetal characteristics of pregnancies
diagnosed with preeclampsia and controls.
Preeclampsia Controls P-value
Number of dyads 528 575 -
Maternal Age (years) 26.3 (7.5) 26.1 (6.2) 0.692
BMI (kg/m2) 26.4 (5.4) 24.5 (4.4) ,0.001
Previous live births 0.80 (1.19) 0.99 (1.08) 0.007
Birthweight (grams) 2805.7 (815.7) 3423.2 (303.0) ,0.001
Gestational age at delivery
(weeks)
36.8 (3.4) 39.7 (1.1) ,0.001
Fetal sex (% female) 45.8 53.3 0.492
Data are presented as means (SD). BMI, body mass index.
doi:10.1371/journal.pone.0016681.t001
COMT Variation and Preeclampsia
PLoS ONE | www.plosone.org 2 January 2011 | Volume 6 | Issue 1 | e16681
(maternal P = 0.034, fetal P = 0.419) was observed to have a
significant effect and was associated with a decreased risk of
preeclampsia (OR= 0.796; 95% CI: 0.646, 0.982). Increased BMI
was associated with an increased risk for preeclampsia
(OR=1.108; 95% CI: 1.076, 1.142) and a larger number of previous
live births decreased the risk for preeclampsia (OR =0.782; 95%
CI: 0.695, 0.880).
Nackley et al. demonstrated in a mammalian expression system
that COMT haplotypes resulted in an ordered progression of
enzyme activity with the ACCG haplotype showing a 18–25 fold
decrease in activity and the ATCA haplotype showing a 2.5–3 fold
decrease in activity compared to the GCGG high activity
haplotype[33]. Results of a multiple logistic regression model that
included maternal and fetal terms to reflect enzymatic activity of
the COMT haplotypes (i.e., each coded as an ordinal variable),
maternal BMI, and previous live births are shown in Table 4.
When maternal and fetal terms were analyzed separately, both
show a significant positive relationship with increasing enzymatic
activity and preeclampsia risk (P =0.003 and P = 0.014 respectively).
However, when both maternal and fetal terms were
included in the same model, again the fetal association decreased
in significance (P =0.561) and the maternal ordered COMT
haplotypes approached significance (P = 0.061).
Obesity is a major risk factor for preeclampsia and our results
demonstrated BMI to be strongly associated with preeclampsia in
this population[48]. COMT metabolizes catecholamines, which
are known to modulate lipid mobilization[49]. Several studies
have found modest associations between obesity and the rs4680
(Val158Met) SNP of COMT[50,51]. The potential for COMT to
contribute to preeclampsia risk through maternal BMI led us to
investigate whether the association between maternal COMT
haplotype and preeclampsia risk in our study could be explained
by a relationship between COMT and BMI. PLINK was used to
test for allelic associations between individual SNPs and BMI,
where BMI was the quantitative phenotype. Haplotype frequencies
were also generated in PLINK based on the four COMT SNPs
and haplotype-specific tests were performed to test for frequency
differences in association with BMI. Table 5 shows results for
analyses that tested the relationship between maternal COMT and
BMI in our study population. No significant associations between
COMT haplotypes or individual maternal SNPs and BMI were
observed.
Table 2. COMT haplotype analysis for mothers and fetuses with and without preeclampsia.
Group Haplotype Frequency Preeclampsia Frequency Controls Chi-square DF P-value
Maternal Global Test 8.260 2 0.016
ATCA 0.373 0.348 1.531 1 0.216
GCGG 0.310 0.277 2.807 1 0.094
ACCG 0.317 0.375 8.112 1 0.004
Fetal Global Test 4.308 2 0.116
ATCA 0.381 0.359 1.302 1 0.254
GCGG 0.302 0.283 0.907 1 0.341
ACCG 0.318 0.360 4.308 1 0.038
COMT haplotype SNP order: rs6269, rs4633, rs4818, rs4680. DF, degrees of freedom. Maternal and fetal samples were analyzed separately. The Global test of association
indicated that, in maternal samples, a significant difference in allele frequencies between cases and controls existed amongst the COMT haplotypes. When haplotypes
were tested individually, both the maternal and fetal ACCG COMT haplotypes were found more frequently in controls than cases.
doi:10.1371/journal.pone.0016681.t002
Table 3. Logistic regression model of primary risk factors for
preeclampsia including presence of the ACCG COMT
haplotype.
Term Estimate (S.E.) P-value Odds Ratio (95% C.I.)
Maternal ACCG 20.228 (0.107) 0.034 0.796 (0.646, 0.982)
Fetal ACCG 20.092 (0.114) 0.419 0.912 (0.729, 1.140)
Maternal BMI 0.103 (0.015) ,0.001 1.108 (1.076, 1.142)
Previous live births 20.246 (0.060) ,0.001 0.782 (0.695, 0.880)
Intercept 22.289 (0.378) ,0.001 -
COMT haplotype SNP order: rs6269, rs4633, rs4818, rs4680. S.E., standard error;
C.I., confidence interval; BMI, body mass index. When both maternal and fetal
ACCG haplotypes from the maternal-fetal dyads were included in a single
model, the maternal ACCG COMT remained significantly associated with
reduced risk for preeclampsia. The fetal ACCG COMT haplotype is not associated
with risk for preeclampsia after correcting for shared genetics between the
mother and fetus.
doi:10.1371/journal.pone.0016681.t003
Table 4. Logistic regression model of primary risk factors for
preeclampsia including COMT haplotype specified according
to reported enzymatic activity.
Term
Estimate
(S.E.) P-value
Odds Ratio
(95% C.I.)
Maternal haplotypes * 0.166 (0.089) 0.061 1.180 (0.992, 1.406)
Fetal haplotypes { 0.052 (0.090) 0.561 1.053 (0.883, 1.257)
Maternal BMI 0.081 (0.019) ,0.001 1.084 (1.045, 1.126)
Previous live births 20.236 (0.076) 0.002 0.790 (0.680, 0.917)
Intercept 22.560 (0.529) ,0.001
COMT haplotype SNP order: rs6269, rs4633, rs4818, rs4680. S.E., standard error;
C.I., confidence interval; BMI, body mass index. Ordered COMT haplotypes:
1 = ACCG/ACCG, 2 = ACCG/ATCA, 3 = ATCA/ATCA, 4 = ATCA/GCGG, 5 = GCGG/
GCGG. Haplotypes were ordered from 1 (low activity) to 5 (high activity) in
accordance with reported information on enzyme activity[33]. Maternal
haplotypes showed increased risk for preeclampsia as haplotypes moved from
low to high activity alleles.
*If maternal term fitted in model without fetal haplotypes P = 0.003, OR = 1.221
(1.073, 1.390).
{If fetal term fitted in model without maternal haplotypes P = 0.014, OR = 1.179
(1.034, 1.345).
doi:10.1371/journal.pone.0016681.t004
COMT Variation and Preeclampsia
PLoS ONE | www.plosone.org 3 January 2011 | Volume 6 | Issue 1 | e16681
The potential for MTHFR to influence risk for preeclampsia
both through a single gene effect and an interaction with COMT
was studied[4,45,47]. The rs4680 loci of COMT encodes for an
amino substitution (Val158Met) and COMT protein with methionine
at position 158 is reported to be less stable and with reduced
activity[32]. However, this instability can be overcome by the
binding of the methyl cosubstrate for COMT, s-adenosylmethionine
(SAM)[52]. MTHFR modulates the availability of methyl
substrates for COMT, including SAM, and the minor ‘‘T’’ allele
of the rs1801133 SNP of MTHFR has been associated with
reduced MTHFR activity and reduced production of SAM[44].
The ATCA haplotype of COMT is the only observed haplotype to
have the ‘‘A’’ allele at the rs4680 loci and we postulated that an
interaction between the ATCA haplotype of COMT and the minor
‘‘T’’ allele of the MTHFR rs1801133 SNP would result in a further
decrease of COMT activity because there would not be adequate
levels of SAM to stabilize the COMT protein. We therefore tested
for epistasis between the ATCA COMT haplotype and SNP
rs1801133 of MTHFR. Results of a multiple logistic regression
model that included maternal and fetal terms for the interaction
between the ATCA COMT haplotype and MTHFR are shown in
Table 6. A significant interaction (P = 0.022) between the fetal
ATCA COMT haplotype and the fetal MTHFR was observed,
which resulted in an increased risk for preeclampsia (OR =1.370;
95% CI: 1.048, 1.792). The critical value for the test statistic
associated with the interaction term was also estimated using
permutation techniques and resulted in an empirical p-value of
0.023. No association was found between SNP rs1801133 in
MTHFR and preeclampsia in either maternal or fetal samples
(P = 0.470 and P =0.225 respectively).
Our results revealed both a maternal protective effect and a fetal
risk effect. Since our data included maternal-fetal dyads, we looked
at the combination of maternal and fetal effects in a single
pregnancy, focusing on the fetal high risk genotypes. Within cases
we looked at the proportion of pregnancies that had two fetal high
risk COMT ATCA x MTHFR ‘‘T’’ combinations with no maternal
protective COMT ACCG allele and those that contained the two
fetal high risk combinations with a balancing maternal COMT
ACCG allele. We observed a higher than expected number of
patients with preeclampsia with both the fetal risk alleles alone
(Chi-square = 3.789; P =0.052) and the fetal risk alleles in
combination with a maternal balancing protective allele (Chisquare
= 22.549; P,0.001). This non-random distribution across
dyads was not observed in controls (P = 0.341 and P =0.219,
respectively).
Discussion
Preeclampsia is a common disorder of pregnancy with potentially
devastating complications[1,53]. Placental hypoxia and
endothelial cell dysfunction are central features of this disorder[
12]. One proposed mechanism for preeclampsia is placental
hypoxia-driven imbalance of angiogenic and anti-angiogenic
factors[12,18,19,21–24], resulting in endothelial dysfunction[
16,18–20,54]. 2-Hydroxyestrogens are metabolized by
COMT to produce 2-ME, a compound with diverse biological
activities including inhibition of HIF-1a, a transcription factor that
mediates cellular response to hypoxia[26–28]. Epidemiologic data
has consistently demonstrated a strong genetic susceptibility to
preeclampsia and COMT has been identified as a candidate gene
for preeclampsia studies[2,3,27,55]. In the present study, we found
that the maternal ACCG haplotype of COMT, which is associated
with low enzyme activity, was associated with a significantly
Table 5. Maternal COMT analysis for body mass index.
COMT Estimate (S.E.) P-value
SNP rs6269 0.120 (0.231) 0.605
rs4633 20.182 (0.222) 0.413
rs4818 0.092 (0.234) 0.693
rs4680 20.192 (0.223) 0.390
Haplotype ATCA 20.191* 0.392
GCGG 0.114* 0.628
ACCG 0.093* 0.675
Estimate is reported with (Standard Error) for SNPs.
*Standard errors are not calculated for haplotypes by PLINK. COMT haplotype
SNP order: rs6269, rs4633, rs4818, rs4680. S.E., standard error; SNP, single
nucleotide polymorphism.
doi:10.1371/journal.pone.0016681.t005
Table 6. Logistic regression model of COMT-MTHFR interaction risks for preeclampsia.
Term Estimate (S.E.) P-value Odds Ratio (95% C.I.)
Maternal ACCG 20.220 (0.126) 0.080 0.803 (0.627, 1.027)
Fetal ACCG 20.126 (0.134) 0.345 0.882 (0.678, 1.146)
Maternal ATCA 0.017 (0.173) 0.921 1.017 (0.725, 1.428)
Fetal ATCA 20.323 (0.174) 0.064 0.724 (0.515, 1.018)
Maternal MTHFR 20.038 (0.143) 0.792 0.963 (0.727, 1.274)
Fetal MTHFR 20.084 (0.145) 0.563 0.919 (0.692, 1.222)
Maternal ATCA: Maternal MTHFR 20.028 (0.138) 0.840 0.972 (0.742, 1.274)
Fetal ATCA: Fetal MTHFR 0.315 (0.137) 0.022 1.370 (1.048, 1.792)
Maternal BMI 0.102 (0.015) ,0.001 1.107 (1.075, 1.140)
Previous live births 20.252 (0.060) ,0.001 0.777 (0.691, 0.874)
Intercept 22.082 (0.437) ,0.001 -
COMT haplotype SNP order: rs6269, rs4633, rs4818, rs4680. MTHFR SNP rs1801133. S.E., standard error; C.I., confidence interval; BMI, body mass index. An interaction
between the fetal ATCA COMT haplotype and the minor ‘‘T’’ allele of MTHFR significantly increased the risk for preeclampsia; after correcting for risk factors identified to
modulate risk in this population.
doi:10.1371/journal.pone.0016681.t006
COMT Variation and Preeclampsia
PLoS ONE | www.plosone.org 4 January 2011 | Volume 6 | Issue 1 | e16681
reduced risk for preeclampsia in this population, and that the risk
increased in a linear fashion from low to high activity alleles. We
also found that epistasis between fetal COMT and MTHFR, which
is associated with decreased enzyme activity as well, was associated
with significantly increased risk for preeclampsia in this population.
We have previously reported that a Comt2/2 mouse model
exhibits a preeclampsia phenotype that is reversed by administration
of 2-ME[27]. This model lead us to postulate that decreased
production of 2-ME in humans, as a result of allelic variation in
COMT, contributed to the development of preeclampsia[27]. The
results of our current study showed that a maternal haplotype of
COMT, which likely results in decreased levels of maternal 2-ME
production, was in fact protective and decreased the risk for
preeclampsia. In contrast, an interaction between a fetal haplotype
of COMT and fetal MTHFR, which likely results in decreased level
of fetal 2-ME production; increased the risk for preeclampsia as
was initially predicted. A significant limitation to the Comt2/2
mouse model is that COMT was absent in both the maternal and
fetal compartments. By being deficient in both compartments, it is
unclear whether the preeclampsia-like phenotype is a result of
deficiencies in both compartments, or rather a deficiency in only
one of the compartments. Although our results appear contradictory
and do not support our initial hypothesis, we would like to
propose that they are not inconsistent with the mouse model. We
speculate that decreased maternal COMT activity would be
beneficial by increasing the production of 2-ME by the placenta
and that a placental loss of COMT activity is the key deficiency
that contributes to the development of preeclampsia.
Previous research on genetic variation in the COMT gene has
largely focused on a single SNP rs4680, which causes a valine to
methionine substitution at position 158 (Val158Met) of the
membrane bound version of the protein and position 108 of the
soluble form. This amino acid substitution has been associated
with a 4-fold decrease in activity in homozygote individuals[32].
Three additional SNPs, rs6269, rs4633, and rs4818, have recently
been reported by Nackley et al. to contribute to haplotype
structures with rs4680[33]. Although only rs4680 encodes an
amino acid change, the additional polymorphisms are predicted to
cause changes in mRNA secondary structure and thus, alter
translation of the gene. Three main haplotypes were identified
GCGG, ATCA, and ACCG and functional analysis in a
mammalian expression system revealed changes in enzyme activity
ranging from a decrease of 2.5–3 fold with the intermediate
haplotype, ATCA, to a decrease of 18–25 fold with the low activity
haplotype, ACCG[33]. Decreased activity of the low ACCG
haplotype was attributed to low translation of the protein, while
the decreased activity of the ATCA haplotype was attributed to
impaired stability of the protein as a result an amino acid
substitution at SNP rs4680[33]. Our study supports this conclusion
in that we found the four SNPs to be in very high linkage
disequilibrium and we identified the same three haplotypes in our
Chilean population. Our single SNP analysis showed no significant
results, but haplotype analysis revealed a significant association
between COMT and preeclampsia.
These results are in agreement with several recent studies that
identified COMT haplotype associations with attention deficit
hyperactivity disorder, pain sensitivity, and Parkinson’s disease[
56–58]. Even more compelling, however, is our finding that
preeclampsia risk changed in a linear fashion when we ordered
haplotypes by reported enzymatic function. The ATCA haplotype
was between the ACCG and GCGG haplotypes, with the ACCG
haplotype being associated with the lowest risk for preeclampsia,
and the GCGG haplotype with the highest risk. This progressive
risk supports the assertion by Nackley et al. that ATCA represents
the intermediate activity haplotype, while ACCG and GCGG are
the extremes[33]. The results reported herein have significant
implications not only for research in preeclampsia, but also for
future studies investigating genetic variation in the COMT gene.
Our results suggest that investigating only the COMT rs4680
Val158Met polymorphism provides incomplete information because
it fails to recognize haplotype structures, which account for
larger variations in enzyme activity. COMT haplotypes therefore
can provide clarification of the role of COMT alleles in disease.
The identification of haplotypes which modulate enzyme activity
to a greater degree than a single polymorphism might explain the
sometimes contradictory results of previous genetic association
studies with other common disease[59,60].
When considering the COMT gene independently, our results
show that the maternal low activity haplotype of COMT, ACCG,
was associated with a significantly lower risk for preeclampsia. The
lower activity of the ACCG COMT haplotype has been reported to
be the result of changes in mRNA secondary structure that lead to
decreased translation of COMT protein[33]. Thus, the protective
maternal effect of COMT on the risk for preeclampsia is likely the
result of a translational mechanism. This significant association
between COMT and preeclampsia highlights the importance of
this gene in preeclampsia, but does not support the causative
mechanism suggested by the Comt knock out mouse. The finding of
a protective effect of a low COMT activity haplotype may suggest
that reduced catecholamine metabolism or 2-ME production in
the maternal compartment spares the placenta from hypoxia.
Decreased metabolism of catecholestrogens in the maternal
compartment would increase the amount circulating through the
placenta and increase the potential production of 2-ME in this
compartment.
Obesity is a major risk factor for preeclampsia and increased
BMI was highly correlated with increased risk for preeclampsia in
our study[48]. COMT metabolizes catecholamines including
dopamine, epinephrine, norepinephrine, and chatecholestrogens.
Catecholamines modulate lipid mobilization by means of adipose
tissue lipolysis[49]. Specifically, estrogen and androgen concentrations
are involved in body fat regulation and estradiol appears
to stimulate preadipocyte proliferation and differentiation. Additionally,
2-ME has been shown to inhibit preadipocyte proliferation
and differentiation in vitro[49]. In 2004, Tworoger et al. found
that the rs4680 SNP in COMT modestly affected exercise-induced
fat loss and in 2008, Annerbrink et al. found that the rs4680 SNP
was associated with increased waist-to-hip ratio and abdominal
sagittal diameter[50,51]. In our study, there was no association
between maternal COMT haplotypes or individual SNPs and BMI
(Table 5). While we can conclude that BMI was not driving the
relationship between COMT and the risk for preeclampsia in the
present study, it is not valid to extend these results past the current
sample since individuals with preeclampsia are oversampled in a
case-control study.
Our COMT x MTHFR interaction findings support a similar
finding by Roffman et al. that the low COMT activity allele was
associated with disrupted prefrontal cortex function only in the
presence of a low MTHFR activity allele [47]. In our study, the
ATCA haplotype of COMT increased the risk for preeclampsia
when the fetus also carried a low activity allele of the MTHFR
gene, characterized by the minor ‘‘T’’ allele at SNP rs1801133.
Unlike the translational mechanism proposed to govern the
maternal COMT effect, the mechanism for the COMT x MTHFR
interaction is most likely to be post translational. The ATCA
haplotype of COMT is the only haplotype that alters the amino
acid sequence and it results in a thermodynamically unstable
COMT Variation and Preeclampsia
PLoS ONE | www.plosone.org 5 January 2011 | Volume 6 | Issue 1 | e16681
COMT protein. However, this instability can be overcome by the
binding of its cosubstrate, S-adenosylmethionine (SAM)[52].
MTHFR modulates the availability of SAM and the minor ‘‘T’’
allele at SNP rs1801133 results in lower production of SAM[44].
Therefore, when the fetus carries the ‘‘T’’ allele of MTHFR and
the ATCA haplotype of COMT, the instability of COMT is not
rectified and lower COMT activity is realized.
The identification of a fetal genetic risk factor for preeclampsia
is an important step in understanding the cause(s) of preeclampsia.
The placenta is fetal tissue and our results strengthen the argument
that primary defects in the placenta play a central role in the
development of preeclampsia. Additionally, our findings are
consistent with the observations of reduced placental COMT
activity and suggest that loss of activity in the fetal compartment of
the Comt2/2 mice appears to be responsible for the development
of disease in this model [27].
Our findings have demonstrated both protective and risk alleles
for COMT in association with the risk for preeclampsia. By
investigating maternal-fetal dyads, we were able to explore the
implications of both, seemingly contradictory, associations in a
single pregnancy. We found a disproportionately high number of
cases with two fetal ATCA COMT x MTHFR ‘‘T’’ risk combinations
and with the two fetal risk combinations and one maternal ACCG
protective COMT allele. What is most striking about our results
however is the much larger chi-square value for the preeclamptic
pregnancies that have two fetal risk combinations and one balancing
maternal protective allele versus only having two fetal risk
combinations and no balancing maternal allele (chi-square 22.549
vs. 3.789). The more significant nonrandom distribution of women
with preeclampsia with a maternal protective ACCG COMT allele
suggests that when the fetus is at high risk, it is preferred to have a
maternal protective ACCG COMT allele to potentially offset the risk
to some degree. Consequently, these pregnancies may be more
viable than pregnancies where the fetus is at high risk, but has no
maternal protection from disease. This hypothesis might help
explain the findings in the Comt2/2 mouse model and the
observation that women with preeclampsia have lower levels of
circulating 2-ME [27]. The balancing combination of maternal and
fetal COMT alleles results in low COMT activity in both the
maternal and fetal compartments and this mimics the low COMT
profile of the knockout mouse. Although our results appear
consistent with the mouse model, further studies are needed to
understand how COMT behaves differently in the maternal and
fetal compartments to modulate the risk for preeclampsia.
Ethnic differences in preeclampsia have been identified.
Increased rates of preeclampsia have been found in African
American, Hispanic, and Asian women compared to white
women, with African Americans having the highest rates[61].
Additionally, maternal-paternal ethnic discordance has been
associated with an increased incidence[61]. These findings
indicate that differences in genetic causes of preeclampsia may
exist between ethnic groups. Global variation in allele frequencies
for both COMT and MTHFR have also been demonstrated
[44,62–67]. Moreover, allele frequencies for both genes are known
to not only differ among major ethnic categories such as
European, Asian, and African American, but substantial variation
has also been demonstrated in subpopulations of each[44,62–67].
Ethnic variation in each gene raises the possibility that different
alleles of COMT and MTHFR could contribute to preeclampsia
risk in different racial groups. The Chilean population in this study
has a genetic background most similar to Western Europeans, and
in particular, those of Spanish decent (2002 census). Future studies
among different ethnic populations are needed to determine if our
results can be extended to other ethnic groups.
Materials and Methods
Ethics Statement
This study was conducted according to the principles expressed
in the Declaration of Helsinki. The study was approved by the
Institutional Review Board of the Virginia Commonwealth
University School of Medicine (IRB # HM12520). All patients
provided written informed consent for the collection of samples
and subsequent analysis.
Study design and population
A case-control study was initiated by searching our clinical
database and bank of biological samples and included Hispanic
women and their neonates in the following groups: 1) Cases –
women with preeclampsia and their neonates (n = 528 dyads); and
2) Controls – women who delivered at term with a normal
pregnancy outcome and their neonates (n = 575 dyads). Participants
received obstetrical care at the So´tero del Rı´o Hospital in
Santiago, Chile (an affiliated of the Pontificia Catholic University
of Santiago, Chile). Exclusion criteria included: (1) known major
fetal anomaly or demise; (2) multi-fetal pregnancy; (3) serious
maternal medical illness (renal insufficiency, congestive heart
disease, etc.); (4) refusal to provide written informed consent; and
(5) a clinical emergency, which prevented counseling of the patient
about participating in the study, such as fetal distress or maternal
hemorrhage. All women provided written informed consent before
collection of the samples. The use of clinical data and collection
and utilization of maternal and neonatal blood for research
purposes was approved by the Institutional Review Boards of the
So´tero del Rı´o Hospital and the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, NIH, DHHS.
Ethnically, the Chilean population is estimated at nearly 95%
white and mestizo (mixed white and Amerindian); 3% Amerindian;
and 2% other. Mixtures between the conquering Spaniards,
largely Andalusians and Basques, and the Mapuches (Araucanians)
produced the principle Chilean racial type (2002 census). There is
no reported evidence to support differences in disease prevalence
amongst Chileans and there is no evidence to support the presence
of group structure within this population. Therefore, population
stratification was determined to not be a source of potential bias in
this study population.
Clinical definitions
Preeclampsia was defined based on the presence of gestational
hypertension (systolic blood pressure $140 mmHg and/or
diastolic blood pressure $90 mmHg) and proteinuria ($300 mg
in a 24-hour urine collection, two or more dipstick measurement
of 1+, or one or more dipstick measurement $2+) according to
ACOG (1) and the National High Blood Pressure Education
Program[1,68]. Patients were considered to have a normal
pregnancy outcome if they did not have any medical, obstetrical,
or surgical complication, and delivered a term neonate ($37
weeks) of appropriate birth weight for gestational age[69] without
complications.
Sample collection
Maternal blood samples were obtained from the mother at the
time of enrollment in the protocol, and from the umbilical cord
immediately after delivery before the detachment of the placenta.
Samples were collected with a vacutainer into tubes containing
EDTA. The plasma tubes were balanced and centrifuged at
1300 g for 10 minutes at 4uC to separate cellular components from
clear plasma, and the samples were stored at 270uC until assay.
COMT Variation and Preeclampsia
PLoS ONE | www.plosone.org 6 January 2011 | Volume 6 | Issue 1 | e16681
DNA extraction
DNA was extracted from maternal and cord blood with a
Qiagen Autopure using standard procedures (Qiagen).
Genotyping
Single-nucleotide polymorphism analysis was performed using
real-time allelic discrimination TaqMan assays (Applied Biosystems)
with modifications. All PCR reactions contained 25–75 ng
of DNA, 6.25 ul TaqMan Universal Master Mix (Applied
Biosystems) (2x), 0.3 ul TaqMan Genotyping Assay (Applied
Biosystems) (20x), and water for a final volume of 12.5 ul. Realtime
PCR was performed on an ABI 7500 Fast Real-Time PCR
Machine (Applied Biosystems) under the following conditions:
50uC for 2 min, 95uC for 10 min, and 40 cycles of amplification
(92uC for 15 sec and 60uC for 1 min). For each cycle, the software
determined the fluorescent signal from the VIC- or FAM- labeled
probe (Applied Biosystems). Allelic discrimination for COMT was
performed using TaqMan Genotyping assays C___2538746_1 for
SNP rs6269, C___2538747_20 for SNP rs4633, C___2538750_10
for SNP rs4818, C__25746809_50 for SNP rs4680 (Applied
Biosystems). Allelic discrimination for MTHFR was performed
using TaqMan Genotyping assay C__1202883_20 for SNP
rs1801133.
Statistical Analysis
Fisher’s exact tests implemented in the PLINK software[70]
were used to test individual SNPs for allelic associations with casecontrol
status and to confirm Hardy-Weinberg equilibrium in the
control group only. Inter-SNP linkage disequilibrium calculations
for COMT were performed in Haploview (version 4.0)[71].
Haplotype frequencies were also generated in PLINK based on
the four COMT SNPs and both global and haplotype-specific tests
were performed to test for frequency differences between disease
status for maternal and fetal samples separately. Haplotypes with
an independent effect were further investigated by multiple logistic
regression in R to condition by covariates known to influence rates
of preeclamsia and to adjust for the correlation between maternalfetal
genotypes. These tests involved assigning haplotypes to
subjects based on the most likely phase reconstructed haplotypes
generated by the expectation-maximization algorithm implemented
in PLINK. An additive term for the haplotype of interest was
coded as 0, 1, or 2 based on copy number present. Based on the
previously mentioned haplotype-specific functional information
from Nackley et al.[33], we also coded COMT haplotypes to reflect
enzymatic activity. COMT haplotypes were sequentially ordered 1
through 5 where 1 was ACCG/ACCG, 2 was ACCG/ATCA, 3
was ATCA/ATCA, 4 was ATCA/GCGG, and 5 was GCGG/
GCGG. Interactive effects between the maternal ATCA COMT
haplotype and maternal MTHFR and the fetal ATCA COMT
haplotype and fetal MTHFR were tested using multiple logistic
regression in R. The MTHFR was included as an additive term
coded as 0, 1, or 2 based on copy number of the minor ‘‘T’’ allele.
Permutation analysis in R with 10,000 iterations was used to
compare models with and without significant interaction terms.
Logistic regression in R was used to test for differences in clinical
characteristics between disease classes for non-genetic variables.
Supporting Information
Table S1 COMT single SNP analysis for maternal and fetal
samples with and without preeclampsia.
(DOC)
Table S2 COMT pair-wise SNP linkage disequilibrium analysis
for maternal and fetal samples.
(DOC)
Author Contributions
Conceived and designed the experiments: JFS LDH TPY LJE. Performed
the experiments: LDH. Analyzed the data: JFS LDH TPY. Contributed
reagents/materials/analysis tools: JPK RG RR. Wrote the paper: LDH
TPY JPK RG LJE RR JFS.
References
1. (2002) ACOG practice bulletin. Diagnosis and management of preeclampsia and
eclampsia. Number 33, January 2002. American College of Obstetricians and
Gynecologists. Int J Gynaecol Obstet 77: 67–75.
2. Chesley LC, Annitto JE, Cosgrove RA (1968) The familial factor in toxemia of
pregnancy. Obstet Gynecol 32: 303–311.
3. Chappell S, Morgan L (2006) Searching for genetic clues to the causes of preeclampsia.
Clin Sci (Lond) 110: 443–458.
4. Goddard KA, Tromp G, Romero R, Olson JM, Lu Q, et al. (2007) Candidategene
association study of mothers with pre-eclampsia, and their infants,
analyzing 775 SNPs in 190 genes. Hum Hered 63: 1–16.
5. Parimi N, Tromp G, Kuivaniemi H, Nien JK, Gomez R, et al. (2008) Analytical
approaches to detect maternal/fetal genotype incompatibilities that increase risk
of pre-eclampsia. BMC Med Genet 9: 60.
6. Zhou Y, Damsky CH, Chiu K, Roberts JM, Fisher SJ (1993) Preeclampsia is
associated with abnormal expression of adhesion molecules by invasive
cytotrophoblasts. J Clin Invest 91: 950–960.
7. Kadyrov M, Schmitz C, Black S, Kaufmann P, Huppertz B (2003) Preeclampsia
and maternal anaemia display reduced apoptosis and opposite
invasive phenotypes of extravillous trophoblast. Placenta 24: 540–548.
8. Kadyrov M, Kingdom JC, Huppertz B (2006) Divergent trophoblast invasion
and apoptosis in placental bed spiral arteries from pregnancies complicated by
maternal anemia and early-onset preeclampsia/intrauterine growth restriction.
Am J Obstet Gynecol 194: 557–563.
9. Brosens I (1964) A Study of the Spiral Arteries of the Decidua Basalis in
Normotensive and Hypertensive Pregnancies. J Obstet Gynaecol Br Commonw
71: 222–230.
10. Brosens I, Robertson WB, Dixon HG (1967) The physiological response of the
vessels of the placental bed to normal pregnancy. J Pathol Bacteriol 93: 569–579.
11. Brosens I (1988) The uteroplacental vessels at term: the distribution and extent
of physiological changes. Trophoblast Res 3: 61–68.
12. Caniggia I, Winter JL (2002) Adriana and Luisa Castellucci Award lecture 2001.
Hypoxia inducible factor-1: oxygen regulation of trophoblast differentiation in
normal and pre-eclamptic pregnancies–a review. Placenta 23 (Suppl A): S47–57.
13. Gervasi MT, Chaiworapongsa T, Pacora P, Naccasha N, Yoon BH, et al. (2001)
Phenotypic and metabolic characteristics of monocytes and granulocytes in
preeclampsia. Am J Obstet Gynecol 185: 792–797.
14. Redman CW, Sargent IL (2003) Pre-eclampsia, the placenta and the maternal
systemic inflammatory response–a review. Placenta 24 (Suppl A): S21–27.
15. Redman CW, Sargent IL (2009) Placental stress and pre-eclampsia: a revised
view. Placenta 30 (Suppl A): S38–42.
16. Roberts JM, Taylor RN, Musci TJ, Rodgers GM, Hubel CA, et al. (1989)
Preeclampsia: an endothelial cell disorder. Am J Obstet Gynecol 161:
1200–1204.
17. Roberts JM, Taylor RN, Goldfien A (1991) Clinical and biochemical evidence of
endothelial cell dysfunction in the pregnancy syndrome preeclampsia.
Am J Hypertens 4: 700–708.
18. Maynard SE, Min JY, Merchan J, Lim KH, Li J, et al. (2003) Excess placental
soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial
dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest 111:
649–658.
19. Levine RJ, Maynard SE, Qian C, Lim KH, England LJ, et al. (2004) Circulating
angiogenic factors and the risk of preeclampsia. N Engl J Med 350: 672–683.
20. Powers RW, Catov JM, Bodnar LM, Gallaher MJ, Lain KY, et al. (2008)
Evidence of endothelial dysfunction in preeclampsia and risk of adverse
pregnancy outcome. Reprod Sci 15: 374–381.
21. Chaiworapongsa T, Romero R, Espinoza J, Bujold E, Mee Kim Y, et al. (2004)
Evidence supporting a role for blockade of the vascular endothelial growth factor
system in the pathophysiology of preeclampsia. Young Investigator Award.
Am J Obstet Gynecol 190: 1541–1547; discussion 1547-1550.
22. Levine RJ, Lam C, Qian C, Yu KF, Maynard SE, et al. (2006) Soluble endoglin
and other circulating antiangiogenic factors in preeclampsia. N Engl J Med 355:
992–1005.
23. Venkatesha S, Toporsian M, Lam C, Hanai J, Mammoto T, et al. (2006) Soluble
endoglin contributes to the pathogenesis of preeclampsia. Nat Med 12: 642–649.
24. Romero R, Nien JK, Espinoza J, Todem D, Fu W, et al. (2008) A longitudinal
study of angiogenic (placental growth factor) and anti-angiogenic (soluble
COMT Variation and Preeclampsia
PLoS ONE | www.plosone.org 7 January 2011 | Volume 6 | Issue 1 | e16681
endoglin and soluble vascular endothelial growth factor receptor-1) factors in
normal pregnancy and patients destined to develop preeclampsia and deliver a
small for gestational age neonate. J Matern Fetal Neonatal Med 21: 9–23.
25. Kusanovic JP, Romero R, Chaiworapongsa T, Erez O, Mittal P, et al. (2009) A
prospective cohort study of the value of maternal plasma concentrations of
angiogenic and anti-angiogenic factors in early pregnancy and midtrimester in
the identification of patients destined to develop preeclampsia. J Matern Fetal
Neonatal Med 22: 1021–1038.
26. Becker CM, Rohwer N, Funakoshi T, Cramer T, Bernhardt W, et al. (2008) 2-
methoxyestradiol inhibits hypoxia-inducible factor-1{alpha} and suppresses
growth of lesions in a mouse model of endometriosis. Am J Pathol 172: 534–544.
27. Kanasaki K, Palmsten K, Sugimoto H, Ahmad S, Hamano Y, et al. (2008)
Deficiency in catechol-O-methyltransferase and 2-methoxyoestradiol is associated
with pre-eclampsia. Nature 453: 1117–1121.
28. Semenza GL (1998) Hypoxia-inducible factor 1: master regulator of O2
homeostasis. Curr Opin Genet Dev 8: 588–594.
29. Lee SB, Wong AP, Kanasaki K, Xu Y, Shenoy VK, et al. (2010) Preeclampsia:
2-methoxyestradiol induces cytotrophoblast invasion and vascular development
specifically under hypoxic conditions. Am J Pathol 176: 710–720.
30. Barnea ER, MacLusky NJ, DeCherney AH, Naftolin F (1988) Catechol-omethyl
transferase activity in the human term placenta. Am J Perinatol 5:
121–127.
31. Sata F, Yamada H, Suzuki K, Saijo Y, Yamada T, et al. (2006) Functional
maternal catechol-O-methyltransferase polymorphism and fetal growth restriction.
Pharmacogenet Genomics 16: 775–781.
32. Mannisto PT, Kaakkola S (1999) Catechol-O-methyltransferase (COMT):
biochemistry, molecular biology, pharmacology, and clinical efficacy of the
new selective COMT inhibitors. Pharmacol Rev 51: 593–628.
33. Nackley AG, Shabalina SA, Tchivileva IE, Satterfield K, Korchynskyi O, et al.
(2006) Human catechol-O-methyltransferase haplotypes modulate protein
expression by altering mRNA secondary structure. Science 314: 1930–1933.
34. Egan MF, Goldberg TE, Kolachana BS, Callicott JH, Mazzanti CM, et al.
(2001) Effect of COMT Val108/158 Met genotype on frontal lobe function and
risk for schizophrenia. Proc Natl Acad Sci U S A 98: 6917–6922.
35. Huber JC, Schneeberger C, Tempfer CB (2002) Genetic modeling of estrogen
metabolism as a risk factor of hormone-dependent disorders. Maturitas 41
(Suppl 1): S55–64.
36. Tai CH, Wu RM (2002) Catechol-O-methyltransferase and Parkinson’s disease.
Acta Med Okayama 56: 1–6.
37. Fan JB, Zhang CS, Gu NF, Li XW, Sun WW, et al. (2005) Catechol-Omethyltransferase
gene Val/Met functional polymorphism and risk of schizophrenia:
a large-scale association study plus meta-analysis. Biol Psychiatry 57:
139–144.
38. Ness RB, Roberts JM (1996) Heterogeneous causes constituting the single
syndrome of preeclampsia: a hypothesis and its implications. Am J Obstet
Gynecol 175: 1365–1370.
39. Di Renzo GC (2009) The great obstetrical syndromes. J Matern Fetal Neonatal
Med 22: 633–635.
40. Romero R (2009) Prenatal medicine: the child is the father of the man. 1996.
J Matern Fetal Neonatal Med 22: 636–639.
41. Fowler B (2005) Homocysteine: overview of biochemistry, molecular biology,
and role in disease processes. Semin Vasc Med 5: 77–86.
42. Ilhan N, Kucuksu M, Kaman D, Ilhan N, Ozbay Y (2008) The 677 C/T
MTHFR polymorphism is associated with essential hypertension, coronary
artery disease, and higher homocysteine levels. Arch Med Res 39: 125–130.
43. Raijmakers MT, Zusterzeel PL, Steegers EA, Peters WH (2001) Hyperhomocysteinaemia:
a risk factor for preeclampsia? Eur J Obstet Gynecol Reprod Biol
95: 226–228.
44. Schwahn B, Rozen R (2001) Polymorphisms in the methylenetetrahydrofolate
reductase gene: clinical consequences. Am J Pharmacogenomics 1: 189–201.
45. Canto P, Canto-Cetina T, Juarez-Velazquez R, Rosas-Vargas H, Rangel-
Villalobos H, et al. (2008) Methylenetetrahydrofolate reductase C677T and
glutathione S-transferase P1 A313G are associated with a reduced risk of
preeclampsia in Maya-Mestizo women. Hypertens Res 31: 1015–1019.
46. Kosmas IP, Tatsioni A, Ioannidis JP (2004) Association of C677T polymorphism
in the methylenetetrahydrofolate reductase gene with hypertension in pregnancy
and pre-eclampsia: a meta-analysis. J Hypertens 22: 1655–1662.
47. Roffman JL, Gollub RL, Calhoun VD, Wassink TH, Weiss AP, et al. (2008)
MTHFR 677C –. T genotype disrupts prefrontal function in schizophrenia
through an interaction with COMT 158Val –. Met. Proc Natl Acad Sci U S A
105: 17573–17578.
48. Walsh SW (2007) Obesity: a risk factor for preeclampsia. Trends Endocrinol
Metab 18: 365–370.
49. Large V, Arner P (1998) Regulation of lipolysis in humans. Pathophysiological
modulation in obesity, diabetes, and hyperlipidaemia. Diabetes Metab 24:
409–418.
50. Tworoger SS, Chubak J, Aiello EJ, Yasui Y, Ulrich CM, et al. (2004) The effect
of CYP19 and COMT polymorphisms on exercise-induced fat loss in
postmenopausal women. Obes Res 12: 972–981.
51. Annerbrink K, Westberg L, Nilsson S, Rosmond R, Holm G, et al. (2008)
Catechol O-methyltransferase val158-met polymorphism is associated with
abdominal obesity and blood pressure in men. Metabolism 57: 708–711.
52. Rutherford K, Bennion BJ, Parson WW, Daggett V (2006) The 108M
polymorph of human catechol O-methyltransferase is prone to deformation at
physiological temperatures. Biochemistry 45: 2178–2188.
53. Sibai B, Dekker G, Kupferminc M (2005) Pre-eclampsia. Lancet 365: 785–799.
54. Roberts JM, Taylor RN, Goldfien A (1991) Endothelial cell activation as a
pathogenetic factor in preeclampsia. Semin Perinatol 15: 86–93.
55. Salonen Ros H, Lichtenstein P, Lipworth L, Cnattingius S (2000) Genetic effects
on the liability of developing pre-eclampsia and gestational hypertension.
Am J Med Genet 91: 256–260.
56. Diatchenko L, Slade GD, Nackley AG, Bhalang K, Sigurdsson A, et al. (2005)
Genetic basis for individual variations in pain perception and the development of
a chronic pain condition. Hum Mol Genet 14: 135–143.
57. Bialecka M, Kurzawski M, Klodowska-Duda G, Opala G, Tan EK, et al. (2008)
The association of functional catechol-O-methyltransferase haplotypes with risk
of Parkinson’s disease, levodopa treatment response, and complications.
Pharmacogenet Genomics 18: 815–821.
58. Halleland H, Lundervold AJ, Halmoy A, Haavik J, Johansson S (2009)
Association between catechol O-methyltransferase (COMT) haplotypes and
severity of hyperactivity symptoms in adults. Am J Med Genet B Neuropsychiatr
Genet 150B: 403–410.
59. Glatt SJ, Faraone SV, Tsuang MT (2003) Association between a functional
catechol O-methyltransferase gene polymorphism and schizophrenia: metaanalysis
of case-control and family-based studies. Am J Psychiatry 160: 469–476.
60. Glaser B, Debbane M, Hinard C, Morris MA, Dahoun SP, et al. (2006) No
evidence for an effect of COMT Val158Met genotype on executive function in
patients with 22q11 deletion syndrome. Am J Psychiatry 163: 537–539.
61. Caughey AB, Stotland NE, Washington AE, Escobar GJ (2005) Maternal
ethnicity, paternal ethnicity, and parental ethnic discordance: predictors of
preeclampsia. Obstet Gynecol 106: 156–161.
62. Sherry ST, Ward MH, Kholodov M, Baker J, Phan L, et al. (2001) dbSNP: the
NCBI database of genetic variation. Nucleic Acids Res 29: 308–311.
63. Palmatier MA, Kang AM, Kidd KK (1999) Global variation in the frequencies
of functionally different catechol-O-methyltransferase alleles. Biol Psychiatry 46:
557–567.
64. Domschke K, Deckert J, O’Donovan M C, Glatt SJ (2007) Meta-analysis of
COMT val158met in panic disorder: ethnic heterogeneity and gender
specificity. Am J Med Genet B Neuropsychiatr Genet 144B: 667–673.
65. Schneider JA, Rees DC, Liu YT, Clegg JB (1998) Worldwide distribution of a
common methylenetetrahydrofolate reductase mutation. Am J Hum Genet 62:
1258–1260.
66. Stevenson RE, Schwartz CE, Du YZ, Adams MJ, Jr. (1997) Differences in
methylenetetrahydrofolate reductase genotype frequencies, between Whites and
Blacks. Am J Hum Genet 60: 229–230.
67. van der Put NM, Eskes TK, Blom HJ (1997) Is the common 677C–.T mutation
in the methylenetetrahydrofolate reductase gene a risk factor for neural tube
defects? A meta-analysis. Qjm 90: 111–115.
68. (2000) Report of the National High Blood Pressure Education Program Working
Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol 183:
S1–S22.
69. Gonzalez RP, Gomez RM, Castro RS, Nien JK, Merino PO, et al. (2004)
[A national birth weight distribution curve according to gestational age in Chile
from 1993 to 2000]. Rev Med Chil 132: 1155–1165.
70. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, et al. (2007)
PLINK: a tool set for whole-genome association and population-based linkage
analyses. Am J Hum Genet 81: 559–575.
71. Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and
visualization of LD and haplotype maps. Bioinformatics 21: 263–265.
COMT Variation and Preeclampsia
PLoS ONE | www.plosone.org 8 January 2011 | Volume 6 | Issue 1 | e16681

Posted by Jeff Schofield DC in 02:17:17 | Permalink | Comments Off

Thursday, June 21, 2012

E-book on Kindle=LET THE FETUS HAVE ITS’ SAY

I haven’t posted in a while because blog.com stopped my readers  comments  from getting to me.  I so enjoyed the feedback.. So I chose to self publish my blog in story form with images and imbedded media for a price of $4.99 on Amazons Kindle Direct Publishing.  I know I have many who love my work and have wanted to support me financially, so I have decided to try and make some money with an e-book.  Since I already have a global following of thankful readers who are notified by my RSS feed when I post, I felt this would be my best place to start marketing my e-book. 

Please buy my e-book and share my 20 year quest with your circle of influence.  The e-book has been edited for grammar and spelling plus I arranged the posts in a timeline.  I also wrote a brief introduction to each of my 39 posts to make it easier to follow the story.  My first post back on Christmas Day 2007 is titled ‘Let the fetus have its’ say! ; so my e-book is listed under that title on Amazon’s KDP.  Just go to Amazon and do a search for this title.  Thanks…

I have continued on my healing quest since my last post titled ‘THE ANUS OF TIME=GROWING OLD TOGETHER’ and my new job is as a farmer in Missouri where me and my 2nd x-wife, JO,  also a Chiropractor, have started a CSA (Community Supported Agriculture) See our website www.twinhavenfarm.com …  We are preparing for the predicted food shortage and growing our own food.  I have lots of garden space planted, about 200 chickens, layers and meat birds, plus 30 acres of land to take care of.  One half is pasture, the other half  is woods plus a small creek flows through the property.

I live very simply and cheaply in my 8×14 camper trailer parked next to the house and plugged into all the utilities, like a cord and placenta.  We have wood heat and I cut and haul the firewood from our woods.   The water is heated by our outdoor wood furnace also.  Still dependent on the electricity though.  I have a dog named buddy after my lost twin sister. So,  life is supporting me to still dig in my prenatal memories.

So, the pain from my latest memories to surface has got me still releasing the pain/pleasure complex in the lowest reaches of my esophagus treated with my dildo and the upper reaches of my nasal passage behind the uvula treated with my thumbs, one side at a time, while stroking the bottom of my penis for the pleasure.  It appears that these two points are the top and bottom of the IUB (In Uterine Breathing mechanism) I have mentioned in earlier posts.  When the pulsing moves through the pain, I just stay still and let the pain guide me into the actual IUB as recorded when this layer of the pain/pleasure complex was imposed either on me or my gene-pool.  The upper nasal cavity trigger points on the right side are tighter than the left, but I still treat both sides to let the light of my heart make peace and harmony with this painful duality in my being.  I have also started eating 8 day old embryonic chicken fetus’s again to help heal the wounded embryonic memories as they surface. These eggs come from our laying hens and I just incubate them 8 days, then blend and freeze them in ice cube trays.  (Chicken Abortions)  I eat one cube a day in a smoothie.  As a first aid kit for any type of skin wound, there is nothing better.  See my you tube video of the chicken embryo at this link.  http://www.youtube.com/watch?v=kYkTePwffD8&feature=plcp   Its all such perfection, this pain/ pleasure complex.                                       All for now, I AM  Jeff Schofield

Posted by Jeff Schofield DC in 17:58:08 | Permalink | Comments Off

Wednesday, November 9, 2011

The Anus of TIME:Growing old together

      I have a friend that constantly questions the validity of the memories awakening inside me.  Recently, she challenged the existence of the pain/pleasure complex which I feel is the result of sex during pregnancy.  She is a nutritionist and is into using food to stay healthy, young and vibrant.   As I thought about her challenge, the idea of “growing old together” came to me.  This is the pain/pleasure complex most geriatric couples are content to accept as a natural cycle of a relationship.  They still “love” each other, yet this love is not sufficient to halt the march of Time, or the “Anus of Time”.  Quite often we refer to someone as an asshole or some other term relating to the anus, (you use your favorite).  The resistance within us all to our anus, (URANUS)  the stinky shit that comes out of it, or whatever, is manifested in our plumbing which takes this main human product to an underground location so we don’t have to smell it.  The placenta is the original place we sent our shit to our mom to deal with it.  Consider the reflection of our original waste treatment facility and the current ones in all our cities.  Womb ecology determines world ecology.  So, how did we as a fetus control the flow of shit to the placenta????  This question has finally got an even deeper answer than ones I have remembered and posted in the past…  The 13  baby chicks I now am raising taught me this answer, or gave me the idea to try within myself when one of them had its poop stick to its peri-anal feathers and the more he/she shit, the bigger the pile of poop got to where the chick was going to die if I didn’t clean its asshole.   So, there I am wetting this clump of fecal material and gently wiping the shit off as it got saturated by the water from the soft cloth I was using to save this chick from a certain demise .. you get the idea… so I am watching the asshole of this baby chick expand and contract with every breath.  I look closer and observe that its asshole isn’t perfectly round, but that it folds over itself and kind of winks like an eyelid every time it breaths.  Wow, I thought it was just a round sphincter muscle like my anus.  But no,  its like my rubbing my lips in and out.  So, where is this going?? Back to the womb and the IUB (inuterine breathing mechanism).  Humans blink over 6 million times a day.  wow,  google it.  Ever since the first time I curled up in a ball with my snorkel in the tub and breathed water up my nose 18 years ago, each time I do it, not only does my naval pulse, but my eyelids have blinked in synch with my naval.  I have asked the question so many times, what does the eye blinking control as far as the umbilical cord is concerned??   Remember I have said that the only thing we did all day long for 9 months was suck/push to maintain the 2 way flow along the umbilical cord.  Well, babies belly breath and then gradually stop.  So as I have remembered the IUB and belly breathing, parts of the puzzle have been masked in the pain/pleasure complex, so I don’t get the whole picture, I just get pieces of it as this awakening of the child within is happeining.  My spiritual guide spoke these words in my mind 18 years ago as I first started this journey, (It’s been 2 million years since anybody opened this vortex).. wow, with stargate and all on TV,  vortex has become a common word.   This vortex is the Anus of Time, or the end of time.  With people blinking 6 million times a day to stir the  memory I refer to, why am I not more poplular on the internet like  many of my readers have commented  I should be.  Well, 2 million years is a long time and if this vortex has remained hidden in the pain/pleasure complex of humanity that long, I shouldn’t expect a support system.  Other than those that comment on my blog, I really have no support system other than the one created out of the resistance to what I am remembering.   Since we are all condemned to repeat that which we can’t remember, I truly feel that we all will remember, that we want to remember, that every ounce of every breath is breathed with the desire to remember, but,  there are dark forces which have blocked our pain with drugs, vaccines, amalgams, chem trails, GMO foods etc…  Pain has been my teacher, friend, support system and the capstone to these fetal memories if you will.  Enough about me.

       So, I discovered on my last trip down my esophagus with my double dildo the “last ring of fire” in the esophageal tissue.  wow, was it painful, way down there, deeper .. As I held pressure for 7 seconds on this trigger point, I percieved the direct connection to my anus/foreskin  embryological mirror image.  Don’t ask me to make sense of it, its just what I percieved.  I found that I could belly breath in a way that I had not consciously experienced before, yet it was the core memory of “growing old together” after  which I have titled this post.  The baby chick I referred to was suck/pushing  its anus like I used to and I found that I could expand and contract my rectum like the baby chick did.  As I did this, the pain/pleasure complex showed me another piece to the puzzle of the IUB.  See, the 2 umbliical arteries come off of the iliac vein in the groin area and the anal suck (expansion)     fills these arteries  like  2 syringes, and the anal  push (contraction) empties the 2 syringes into the umbilical cord as it exits the naval.   The eyelids are blinking in synch with this anal suck/push.  No wonder people hate their crow feet…   The top of the ears rock back and forth, suck/push,  … the eyeballs are connected to the soft palate and do the suck/push in synch with the rectum.  This is just more detail to my original explanations of the IUB in former posts where I simply state that everything in the upper half of the body works together with everything in the lower half of the body to maintain the umbilical cords 2 way flow of blood.  We were in control of this flow until mom and dad had sex and the uterus contracts and nothing will flow in or out of the cord no matter how hard we suck/push, no matter how much apathy, grief, fear, anger,  pain or pleasure we feel.  We are simply “Up Shit Creek without a paddle”. 

     As a chiropractor, I saw the hips rotate this way or that way.  Each of my patients had a little different twist on their pain pattern, yet as I am seeing this new insite to blinking etc, here is the mechanism of spinal misalignment, scoliosis included.    I have been ridiculed, ignored etc ( no support system) by my fellow chiropractors for stating that sex during pregnancy is the origin of most if not all of human suffering. Its ahaaa moments like these when my creator reveals the simplicity of it all to me that makes me feel the journey has been worthwhile.  I have relegated my being acknowledged for my efforts till the end of time.  May it come quickly for us all as that will be the end of human sufferring and bring the peace on earth we all desire..  Kind regards, I AM  Jeff Schofield  DC

Posted by Jeff Schofield DC in 22:16:40 | Permalink | Comments (4)

Wednesday, September 14, 2011

Deep Throat Sex, Fetal Origin

Well, time for another trip into my recently remembered fetal memory.  In prior posts, I talked about using my finger to do trigger point massage on my throat, mouth, and nasal muscles.  By doing one side, then the other of the same muscle on the other side, I was gradually able to tame the gag reflex.  I reason that pain and pleasure are wrapped together in the fetal experience of sex during pregnancy, thus I use masturbation when I feel the need to bring some pleasure into the chore of releasing the tight and painful muscles I find in my mouth, throat and nose.  A little alcohol, Brande, or coffee helps to relax the throat area and eases the pain.  Trigger points exist in all striated muscle including the sphincter muscles of the anus and 3 in the ureter, urethra tract.  I use “urethral sounds” to tame the trigger points in the urethra which have their mirror image   in the throat area.  Ever notice which muscles in your throat area you wiggle around to get an orgasm or to get your pee to release.  Its the same set of muscles and in the womb we didn’t orgasm, yet we pee every thirty minutes after the urinary tract develops.  So, DEEP THROAT SEX…. I was on a porn site and saw a double dildo that lesbians use being inserted by a woman down her throat, that’s 18 inches or so..  I thought, wow, she is really relaxed in her throat.  Having already gone as deeply as I could with my index finger, thoughts of sw0rd swallower’s peaked my curiosity.  I ordered a 18″  double dildo online from a sex toy store.  While waiting, I went to a local porn shop and bought a male dildo about 8 inches long and began exploring my throat, esophagus, for sore trigger points and it didn’t take very long to realize I was in uncharted territory.  Very, very painful trigger points in the esophageal muscles.  I began using kinesiology muscle testing to try and come to some understanding of why these muscles were so tight and painful.   Every thing I eat and drink passes over these muscles.  I have a post called “Anatomic Mirror Images” I suggest you read to understand what the embryological mirror image of the deep throat area is, but in males its the foreskin that was cut off when I was circumcised.  Circumcision of females occurs in some cultures also.  Its called Female genital mutilation.  If you have never watched a baby boy being circumcised, please go to YouTube and watch one.  Its such a barbaric act of cruelty to this helpless baby.  That memory is perfectly recorded in the esophageal mirror image of the foreskin.   Alcohol, coffee, chewing tobacco, all the many stimulants effect this mirror image of our foreskin.  Anyway, I have been gradually. 2 times a week, using this double dildo to “treat” the chronically painful muscles of the esophagus.  The Gag reflex and vomiting are just part of the adventure.  The reward is that these painful esophageal muscles relax and release so much stress, tension etc which is followed by increased sensual feelings releasing.  The shy, conservative nature is overcome.  I feel many sexual problems have their roots here and encourage my readers to try it.  Just remember to only give yourself as much pain as you can willingly and lovingly endure as love conquers all, even pain.  For more understanding of this principle, study the principles on the body electronics website, www.howweheal.com where pain is known as the capstone to memory.  The sexual energy is the resurrectional energy and when mastered is said to rejuvenate the body to a youthful state.  The False Gods mentioned in the Oahspe Bible that “inspired” the use of circumcision are to blame for the origins of the cruel practice of circumcision and its painful memory which effectively blocks the majority of humanity from remembering the prenatal memories of sex during pregnancy mentioned in my  blogs other posts.  Many of my readers have wondered why I am not more popular or why I don’t take donations or sell an  e-book,,,, well, its because pain is not popular and pain has been my teacher.   I am sharing how you can free yourself from the chains of pain, sickness and death as a glad free gift as  health is your wealth.  I may write a book, who knows?  If I was popular, I wouldn’t have the time or energy to keep remembering as folks would want me to lecture, travel etc, so I depend on you to take responsibility, heal yourself, and most of all ,, share this information freely with your circle of influence.  There were no clothes in the Garden of Eden…Kind regards, Jeff Schofield DC

Posted by Jeff Schofield DC in 19:40:39 | Permalink | Comments (29)

Wednesday, June 29, 2011

Fetal Twist of Fate

Twisting, turning, wiggle room, escape, running, faster and faster we go through life thinking we can get away from our pain.  Just like we did in the womb, yet, we keep repeating our patterns..  The hands of a fetus look like the twisted hands of a geriatric.  The wrist can twist right and left.  My friend Tom was unable to make a fist and flex his wrists down when tested for entrance into the army.  A defect they said.. He is very mechanically gifted, knows his motors, bikes and cars like the back of his hand.  My oldest daughter Jennifer has her right hand twisted in the classic pattern of Cerebral Palsy.   In reflexology, there are heart points on the palm of the hand and arch of the foot which were a very subtle part of the twist I am referring to.  These points will pulse in synch with my naval when I go down under and draw urine across my nasal membrane.  The gradual killing of the little child inside that occurs each time the fetus experiences the suffocation of maternal orgasm creates such a wide variety of physical, mental and emotional defects in each  of us that we think its normal..  Death by natural causes..  Aging and Death are a perfect reflection of the gradual killing or as they call it in psychological circles, programming, of the original perfect DNA intended by our creator to not be subject to death. 

Here is my point, I have experienced that the simple twisting of the wrist back and forth along with the feet inverting and everting was a survival mechanism to regain control  of the cord blood flow when orgasm occurs. I can feel the connection to my heart pain I have felt for years as I twist my left wrist ever so slightly back and forth as I am curled up in the bathtub.  It is incredibly relaxing, like an entire other side to myself that I have been resisting as the original memory is one of pain and pleasure wrapped together.   Its analagous to putting our own twist on events to make us look right, to get things our way, my way or the highway, get out of my way, I am right because I am bigger, as that was how we would live.. Thats why some people hate to be questioned or challenged, they must always be right.  The spin that a reporter can put on a story to make one way right and the other way wrong all goes back to the fetal twist of the wrist.  Thats how we survived in the womb, writing our story on the DNA of our body.  Everything each of us needs to know is written in our hearts if you will..   Is it any wonder that the huge amounts of time spent on video games  involve only  slight movements of the hands and wrist, this is not dissimilar to our modern cars which almost drive themselves except for an occasional twist this way or that of the steering wheel.  Subconsciously, we simply want to remember the way we were in the womb. 

So for you doubting my word, test it yourself.  Go within and ask if this applies to you.  I feel that the light in each of us is the same and what makes us all unique is how we have qualified that light from conception to the present.  The earlier memories in the womb are by far the most influential in making up our individuality, yet the light of our Creator shines through it all.  I have a deep groove on the right eyebrow compared to my left so I figure that sometime in the womb, I was sucking harder on the right side as the left side was plugged with shit from a former sex education bout with my parents… There is something that is balancing between my right and left side that is very exciting to me and it is so subtle that it is hard to put into words.  I have tried and hopefully it will be of use to you in your journey.  Kind regards & happy twisting, Jeff

Posted by Jeff Schofield DC in 03:45:38 | Permalink | Comments (106)

Sunday, May 29, 2011

My lost twin sister, my buddy…

I have mentioned my twin sister in a former post  ” Confronting Shames Origin” but with recent experiences in remembering my prenatal experience, I have decided to make a post in her honor.   Always searching for that perfect mate in my 4 marriages and numerous intimate lovers, I have come to understand that these experiences were created by myself to help me remember, honor and acknowledge “my buddy”.  The feeling of closeness my buddy gave me early on in the womb and which ended rudely when my parents had sex and my buddy died and then left, has been the same pattern I have created in all my female relationships.  They must go away by divorce, anger, fear, intimidation, emotional starvation, etc as that was the same pattern as my original script in the womb where I spent 3 blissful months alongside my buddy and then she died and left a few days later.   The deeper I dig into my prenatal memories using the techniques outlined in former posts, the clearer it becomes that I am living out in this dimension the scenes that transpired in the womb dimension.  The biggest coverup of the pain/pleasure complex by humanity is that sex during pregnancy is not felt and experienced as pain and pleasure wrapped together.  An honest assesment of relationships in marriage or otherwise always has pain and pleasure in it.  Every love song, love story, poetry, art or emotionally creative activity expresses this deepest of memories.  Elvis Presley was a twin survivor and look at the songs he created to signify this reality of human experience.  My buddy deserves the highest place of honor, respect and dignity in my consciouness in order to heal myself.  To directly tune into my creator, the I AM presence, which was with me the entire journey in the womb up to the present.  The pain/pleasure complex of sex during pregnancy created a block in my being which confused me as to who  I AM, what my relationship is to the world, my buddy, my parents, my creator, etc.   I have spent the past 18 years digging in my prenatal memories because my creator, my heavenly father, the source of my being, the light that lighteth every man/women that cometh into the world, wants me to willingly hear and follow his voice.  His voice is clouded by the traditions of the fathers, specifically sex during pregnancy.  The Oahspe Bible clearly reminds humanity that sex during pregnancy is a violation of his commandment.  (See my former post Oahspe 8 commandments). 

        So, dear buddy, this post is for you.  I hope that your memory in me will touch that same memory in my readers who experienced losing their twin inutero.  Lately, I have been reading several books on “Vanishing Twin Syndrome” .  I could list them, but leave that journey and responsibility with you.  Just do a google search and it will open a new world to you of the large number of people who are waking up to the memory of losing a twin in the womb.  The awakening on the planet  to the light of our creator is the melting away of the Pain/Pleasure complex and everyone of us will eventually remember or die.  The death and dying process is a perfect reflection of this pain/pleasure complex.  As the aging process progresses, the mass unconsciousness to the prenatal memories expresses perfectly as the body curls back into the fetal postion and the pain regains its place after years of attempted suppression of the pain with only the pleasure as the desired goal..  The song “Memories” has a beautiful line, “Whats too painful to remember, we simply choose to forget, so its the laughter, we will remember, whenever we remember, the way we were”…. So its those painful memories we have forgotten in the womb that express themselves in the wrinkles, gray hair, tooth decay, wasting muscles, arthritis….. etc, the supposed death by natural causes…. For those of you familiar with the teachings of Saint Germaine, he states that over 90 percent of the aging process is caused by misuse of the sexual energy and blames the Doctors for the lies that sex during pregnancy is safe for the fetus..  The pharmaceutical industry is our own creation due to our resistance to pain and the cellular memory of conception when the magic pill syndrome was implanted in our psyche. 

        I want to acknowledge the subltle feelings of loneliness, depression, fear, anger, apathy, grief, pain etc… that have been hard to understand until I got in touch with the actual memory of being a twin, acknowledging my twinship, no longer trying to replace my buddy with another female.   One of the books I read talked about dolls, teddy bears etc as childhood ways of expressing twinship, so the other day I was walking up the alley and found a disgarded 6 inch maroon teddy bear with a red chrystal glass heart pendant on its chest.  I have adopted this little buddy and it now has a place of honor on my pillow or nightstand.  When I look at this symbol of my lost twin sister, it gives me incredible comfort to have something to project these formerly unanswered feelings and thoughts into.  Even as I right this post, its feels like the words are coming from a very deep and holy place in my heart which is the resting place of my lost twin sister.  Only I acknowledge her existance as my parents didn’t know she ever existed.  They killed her by following the tradition of their parents of sex during pregnancy.  As my buddy died, then was slowly reabsorbed and lost by 3 days of bleeding which my mother acknowledges happened at the beginnning of the 4th month of pregnancy,  I feel that the cellular material of the placenta became a part of my body.  I have some well placed warts right in the middle of key areas of the pain patterns that I am loving which I am feeling are the only tangible evidence of my twin sister in my body.  There are numerous reports in the medical literature of teratomas in a twin which when surgically removed have hair, teeth, bones etc in the tumor which is a good indication that warts could also be  twin leftovers..  I ate my twin sister,  the tradition to not leave any food on your plate, no food on your mouth while eating, maybe is a reflection of these early memories of eating in the womb where the struggle for survival was a life and death scenario.  Hunger pain and its origins from these prenatal struggles for nourishment was a litteral battle in which one must die for the other to live.  The suck/push battle for uterine blood supply the twins engaged in .. so many explanations for the proper social ettiquette when eating..  Lots to think about…

    Well, dear buddy, I am finished with this post.

Posted by Jeff Schofield DC in 15:52:50 | Permalink | Comments (128)

Monday, March 14, 2011

HEY BABE, YA WANNA SUCK FACE

I laughed so hard when this ahah moment came, picture this, 2 naked bodies with their cord and placentas still attached with the placentas plastered on the other persons face, sucking face.  So often, kissing, making out, french kissing etc are also referred to as sucking face.  The exchange of bodily fluids, all the meridians of the energy body entangled in this thing we call “making love”.  So just what is it we’re doing when we feel time stand still when we are with someone in the sexual act with all its various levels of manifestation.  Its just one memory fueling it all, the memory of our first experience with the sexual energy in the womb.  There we were, curled up in a ball, suck/pushing for all we are worth to try and maintain the flow of blood while the memory of the inevitable  maternal orgasm, which stops the blood flow  carrying fresh oxygen,  lingers in our fucked up fetal mind from past sex education bouts with mom and dad.  Let me throw in a very recent scientific article from pub med admitting that pre-eclampsia is caused by placental  ischemia and hypoxia. ( Ischemia means loss of blood flow and hypoxia means a lack of oxygen. )

Expert Rev Obstet Gynecol. 2010 Sep 1;5(5):557-566.

Recent insights into the pathophysiology of preeclampsia.

George EM, Granger JP.

Department of Physiology and Biophysics and the Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS 39216, USA.

Abstract

Preeclampsia, characterized by new-onset gestational hypertension and proteinuria, is a common and serious complication of pregnancy. Evidence from both animal and human studies has implicated placental ischemia and hypoxia as a central causative factor in the etiology of the disorder. The ischemic placenta in turn initiates a cascade of secondary effector mechanisms, including altered proangiogenic and antiangiogenic factor balance, increase in maternal oxidative stress and endothelial and immunological dysfunction. The full elucidation of these mechanisms will hopefully lead to a more complete understanding of the etiology of preeclampsia and lead to successful therapeutic intervention through the targeted disruption of new and novel pathways.

PMID: 21170149 [PubMed]PMCID: PMC3001629 [Available on 2011/7/1]

      This is love, no way can we question it as it was programmed over and over again while we were in the womb.  Even Scientists, this close to the truth can’t see it as its burried in their own subconscious mind which they can’t see, and seeing is believing in Science.  “The blind shall lead the blind and they shall both fall in the ditch.”   

     Remember I told you about the ryhthmic expansion and contraction of the pharyngeal space that ultrasound has revealed the fetus doing?  This is the suck/push of sucking face.  Often the term, come up for air, is used after locking lips for an extended period of time.  This air would not be mixed with the energies of the person you were locking lips with so the phrase is interesting.  Look at the location of hickies on the throat under the jaw, this is the pharyngeal space, or as close as one can get to it from the outside, its also the location generally acknowledged by vampires as being the place to strike. 

      This is the puppy love, the love sickness, the heartache of all our lovesongs.  Especially country music has its roots based in 2 is company, 3 is a crowd consciousness.  We want the pleasure without the pain, but it never works that way as we are all following the script from the womb when mom, dad and the baby are the 3 is a crowd.  The baby carries that into life and when its old enough to activate its sexual energy at puberty, then the pain/pleasure script of the womb reveals itself.  We keep butting our head against the reality that sex during pregnancy fucks us up, feels so good, then the pain comes and we split up with our lover.   We find a 3rd party to fill out the love triangle in extramarital relations.  Bill Clinton, your my hero. 

    This imagery of 2 naked bodies sucking each others face with their placentas could be any mixture of gender, age or race and would encompass all the diverse ways that humanity is expressing its sexuality.  Whether as homesexual, lesbian, child molestation by Catholic priests, rape, incest, autoerotic asphyxiation, tantric sex,  monogamy, polygamy, doesn’t matter, its all the same fetal memory awakening within us of the pain and pleasure wrapped together.  If anyone reading this has a talent for creating a visual image of sucking face and wants to donate your work, I will post it with this post.  Just send it to my email as an attachment with the subject “sucking face”.  My email is jschofield4u@yahoo.com  .  For centuries, sex during pregnancies influence has stayed suppressed in our bodies, but the end of time is flushing these prenatal memories to the surface and the conservative types keep trying to suppress it while those of us with souls tired of the lie are awakening to the end of time, the end of death, the rebirthing of life as our creator intended.   Remember, the end of time is nothing more or less than the collective remembering of all we have experienced from conception to the present.

    The tsunami in Japan awakens the deep seated fear of suffocation we all experienced in the womb during maternal orgasm.  Maybe mother earth gave us a message or, more likely,  maybe the illuminati caused mother earth to give us a message via HAARP. http://www.ufo-blogger.com/2011/03/japan-earthquake-tsunami-haarp.html         Judging from the videos and newscasting, this will be old news soon..  What will it take to get humanity to stop fucking the fetus???  I have labored on this website to bring provacative thoughts to my readers, yet, I feel I am making little headway in consciousness change that will end sex during pregnancy.  If you can help in any way you feel, it is much apprectiated by all the suffocated fetal memories within us all that scream for freedom from the lie of all lies that brought death to this planet, ie sex during pregnancy is safe for the fetus..  We have been doing it so long, its analogous to the tinman on the Wizard of Oz when he let his ax down after Dorothy and the Scarecrow oiled his rusted arm,  Remember, he said ” I’ve been holding that ax up for the longest time”  like we have forgotten the law of our creator to not have sex during pregnancy.  We have rusted in the pattern that it is OK.  Just look at all the  other animals, they only have sex for procreation. Did you know that a pregnant mare will attack a stallion with her hoofs if he tries to mount her?  This is horsepower at its finest… If you havn’t yet, check out my heroic chicken embryo on you tube as it challenges the medical dogma that sex during pregnancy is safe.   http://www.youtube.com/watch?v=kYkTePwffD8   Remember, animals don’t lie so if you think I am lying, trust the animals.   Trust your gut feeling.  :)

Posted by Jeff Schofield DC in 21:56:18 | Permalink | Comments (86)