Open Access Highly Accessed Research article

Variation in endoglin pathway genes is associated with preeclampsia: a case–control candidate gene association study

Mandy J Bell12*, James M Roberts2345, Sandra A Founds12, Arun Jeyabalan23, Lauren Terhorst1 and Yvette P Conley1

Author Affiliations

1 University of Pittsburgh School of Nursing, 3500 Victoria Street, 440 Victoria Building, Pittsburgh, PA, 15261, USA

2 Magee-Womens Research Institute and Foundation, 204 Craft Avenue, Pittsburgh, PA, 15213, USA

3 Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, USA

4 Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA

5 University of Pittsburgh Clinical and Translational Research, Pittsburgh, PA, USA

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BMC Pregnancy and Childbirth 2013, 13:82  doi:10.1186/1471-2393-13-82

Published: 1 April 2013

Abstract

Background

Preeclampsia is a hypertensive, multi-system pregnancy disorder whose pathophysiology remains unclear. Elevations in circulating soluble endoglin (sENG) and placental/blood ENG mRNA expression antedate the clinical onset of preeclampsia. This study investigated if endoglin (ENG) pathway genetic variation was also associated with the development of preeclampsia.

Methods

We used a case–control candidate gene association design. Data from 355 white (181 preeclampsia cases/174 controls) and 60 black (30 preeclampsia cases/30 controls) women matched on ancestry, age, and parity were analyzed. Tagging single nucleotide polymorphisms (tSNPs) and potentially functional SNPs in ENG, TGFβ1, TGFβR1, ALK1, and TGFβR2 were genotyped with iPLEX® and TaqMan®. Chi-square or Fisher’s exact tests were used to conduct allele/genotype/haplotype tests in white/black subgroups separately. Odds ratios were computed with binary logistic regression for tSNPs with significant genotype tests.

Results

Of the 49 SNPs evaluated, variation in two ENG tSNPs (rs11792480, rs10121110) and one TGFβR2 tSNP (rs6550005) was associated with preeclampsia in white women (P <0.05, each). In black women, variation in two TGFβ1 tSNPs (rs4803455, rs4803457), one TGFβR1 tSNP (rs10739778), and three TGFβR2 tSNPs (rs6550005, rs1346907, rs877572) was associated with preeclampsia (P <0.05, each). Further evaluation of ENG tSNP rs10121110 revealed that white women inheriting the AA genotype were 2.29 times more likely to develop preeclampsia compared to the GG genotype (P = 0.008, [99% CI: 1.02 to 5.13]). For black women, similar evaluation of TGFβ1 tSNP rs4803457 revealed women inheriting the CT genotype were 7.44 times more likely to develop preeclampsia than those with the CC genotype (P = 0.005, [99% CI: 1.19 to 46.41]).

Conclusions

ENG pathway genetic variation is associated with preeclampsia. Different ENG pathway genes may be involved in preeclampsia development among white and black women. Additional studies are needed to validate these findings and to determine if genetic variation in ENG pathway genes impacts ENG and sENG levels in preeclampsia.

Keywords:
Endoglin; Genetic association study; Preeclampsia; SNP