Skip to main content

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

TitleVariation in endoglin pathway genes is associated with preeclampsia: a case-control candidate gene association study.
Publication TypeJournal Article
Year of Publication2013
AuthorsBell, M, Roberts, J, Founds, S, Jeyabalan, A, Terhorst, L, Conley, Y
JournalBMC Pregnancy Childbirth
Volume13
Pagination82
Date Published2013 Apr 01
ISSN1471-2393
KeywordsActivin Receptors, Type II, Adult, African Continental Ancestry Group, Antigens, CD, Case-Control Studies, Endoglin, European Continental Ancestry Group, Female, Gene Expression, Haplotypes, Humans, Polymorphism, Single Nucleotide, Pre-Eclampsia, Pregnancy, Protein-Serine-Threonine Kinases, Receptor, Transforming Growth Factor-beta Type I, Receptor, Transforming Growth Factor-beta Type II, Receptors, Cell Surface, Receptors, Transforming Growth Factor beta, Signal Transduction, Transforming Growth Factor beta1, Young Adult
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.

DOI10.1186/1471-2393-13-82
Alternate JournalBMC Pregnancy Childbirth
Citation Key625
PubMed ID23548068
PubMed Central IDPMC3651360
Grant ListP01HD30367 / HD / NICHD NIH HHS / United States
UL1 TR000005 / TR / NCATS NIH HHS / United States
5M01RR00056 / RR / NCRR NIH HHS / United States
P01 HD030367 / HD / NICHD NIH HHS / United States
T32 NR009759 / NR / NINR NIH HHS / United States
T32NR009759 / NR / NINR NIH HHS / United States
1F31NR011379 / NR / NINR NIH HHS / United States
F31 NR011379 / NR / NINR NIH HHS / United States