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GENOMICS OF ENDOGLIN PATHWAY IN PREECLAMPSIA

Bell, Mandy J. and Conley, Yvette P. and Roberts, James M. and Founds, Sandra A. and Terhorst, Lauren (2012) GENOMICS OF ENDOGLIN PATHWAY IN PREECLAMPSIA. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

THE GENOMICS OF ENDOGLIN PATHWAY IN PREECLAMPSIA
Mandy J. Bell, PhD, RN
University of Pittsburgh, 2012

Preeclampsia is a pregnancy disorder that greatly impacts maternal and fetal/neonatal health and wellbeing. This case-control candidate gene association study investigated endoglin pathway genetic variation and its association with preeclampsia. Tagging single nucleotide polymorphisms (tSNPs) in ENG, TGFβ1, TGFβR1, ALK1, and TGFβR2 were genotyped with iPLEX® and TaqMan® in maternal/fetal dyads. The Prenatal Exposures and Preeclampsia Prevention study provided maternal DNA extracted from peripherally collected white blood cell pellets, along with umbilical cord serum we used for fetal DNA extraction. Data on 355 white (181 cases/174 controls) and 60 black (30 cases/30 controls) women matched on ancestry, age, and parity were analyzed. Separate subgroup allele/genotype/haplotype tests were conducted with Chi-square or Fisher’s exact tests. Binary logistic regression provided odds ratios for tSNPs with significant genotype tests. Analysis of maternal/fetal dyads was not conducted, because unlike the maternal samples, the fetal samples did not provide a quality template suitable for iPLEX® data collection. In white women, variation in ENG (rs11792480, rs10121110) and TGFβR2 (rs6550005) was associated with preeclampsia. Allelic frequency distributions in rs11792480, rs10121110, and rs6550005 were significantly different among cases and controls while genotype distributions of rs10121110 and rs6550005 were further associated with preeclampsia (p-values < .05). For rs10121110, women with the AA genotype were 2.290 times more likely to develop preeclampsia compared to the GG genotype (99% CI [1.022, 5.133], p = .008). ENG haplotype TACGA, which contains rs11792480 and rs10121110 risk alleles, was also over-represented in cases (p = .022). In black women, variation in TGFβ1 (rs4803455, rs4803457), TGFβR1 (rs10739778), and TGFβR2 (rs6550005, rs1346907, rs877572) was associated with preeclampsia. Allelic frequency distributions in rs10739778, rs6550005, rs1346907, and rs877572 were significantly different among cases and controls while genotype distributions of rs10739778, rs4803455, and rs4803457 were further associated with preeclampsia (p-values < .05). For rs4803457, women with the CT genotype were 7.437 more times likely to develop preeclampsia compared to the CC genotype (99% CI [1.192, 46.408], p = .005). These results demonstrate that variation in ENG pathway genes is associated with preeclampsia, with different genes from the same pathway contributing to preeclampsia in white compared to black women.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Bell, Mandy J.mjb111@pitt.eduMJB111
Conley, Yvette P.yconley@pitt.eduYCONLEY
Roberts, James M.robertsjm@mwri.magee.edu
Founds, Sandra A.foundss@pitt.eduFOUNDSS
Terhorst, Laurenlat15@pitt.eduLAT15
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairConley, Yvette P.yconley@pitt.eduYCONLEY
Committee MemberRoberts, James M.robertsjm@mwri.magee.edu
Committee MemberFounds, Sandra A.foundss@pitt.eduFOUNDSS
Committee MemberTerhorst, Laurenlat15@pitt.eduLAT15
Date: 24 July 2012
Date Type: Publication
Defense Date: 22 May 2012
Approval Date: 24 July 2012
Submission Date: 19 July 2012
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Number of Pages: 145
Institution: University of Pittsburgh
Schools and Programs: School of Nursing > Nursing
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: preeclampsia, endoglin, genetics, genetic association, SNP
Date Deposited: 24 Jul 2012 15:57
Last Modified: 24 Jul 2017 05:15
URI: http://d-scholarship.pitt.edu/id/eprint/13013

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