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(Unpublished)
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: |
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ETD Committee: |
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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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