eNOSI4 and EPHX1 polymorphisms affect maternal susceptibility to preeclampsia: analysis of five polymorphisms predisposing to cardiovascular disease in 279 Caucasian and 241 African women
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- Groten, T., Schleussner, E., Lehmann, T. et al. Arch Gynecol Obstet (2014) 289: 581. doi:10.1007/s00404-013-2991-9
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The aim of this study was to evaluate possible associations of genetic polymorphisms predisposing to cardiovascular disease with the development and/or the severity of preeclampsia.
A two hospital-based prospective case–control study was performed in Germany and Ghana. 470 blood samples of 250 Caucasian and 220 black African have been genotyped by pyrosequencing and fragment length analysis. We evaluated the distribution of the epoxide hydrolase 1 (EPHX1) polymorphism on exon 3, the endothelial nitric oxide synthase (eNOS) polymorphisms on exon 7 and on intron 4, the angiotensinogen polymorphism on exon 2 and the estrogen receptor 1 polymorphism in intron 1.
74 Caucasian and 84 African were classified as preeclampsia with 27 Caucasian developing a hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome and 17 African women experiencing eclampsia. Multivariate logistic regression analysis adjusting for ethnicity, age and parity revealed for carriers of eNOSI4 VNTR4a a 1.7-fold increased (95 % CI 1.10–2.711, p = 0.016) risk to develop preeclampsia and a 3.6-fold increase for carriers of the EPHX1 113Tyr (95 % CI 1.366–8.750, p = 0.009) to develop severest preeclampsia.
Our finding of eNOSI4 polymorphism predisposing to preeclampsia independently of ethnicity, age and parity supports the concept of NO being involved in the endothelial disorder preeclampsia. Since EPHX1 is highly expressed in the liver, can interact with various signaling pathways and is involved in central nervous system disorders, the association of EPHX1 polymorphism with the HELLP syndrome and eclampsia may hint to EPHX being a further key player in the pathogenesis of preeclampsia.