Preeklampside ve Gestasyonel Hipertansiyonda CYP4F2, 4F3, 4A11, 2J2, 2C9, 2C19 ve Solubl Epoksit Hidrolaz Enzimlerinin Genetik Polimorfizmlerinin Etkileri

Abstract

Preeclampsia and gestational hypertension (GH) are disorders that may cause morbidity and mortality in both mother and infant. The pathophysiologies of both disorders have not been clearly established. Early detection and close follow-up of patients with high risk for preeclampsia and GH is important. Genetic factors play a major role in development of preeclampsia and GH. Detection of genetic polymorphisms that may play role in these disorders may help clarify the pathophysiology and can be useful for early diagnosis and treatment. 20-hydroxyeicosatetraenoic acid (20-HETE) is an endogenous vasoconstrictor substance also responsible for inhibition of trophoblast migration, endothelial dysfunction and hypertension. CYP4F2, CYP4F3 and CYP4A11 enzymes metabolize arachidonic acid to 20-HETE. Epoxyieicosatrienoic acids (EET) have vasodilator and anti-inflammatory activities. CYP2J2, CYP2C9 and CYP2C19 are responsible for the formation of EET, which are metabolized by the soluble epoxide hydrolase enzyme to the less active metabolite dihydroxyeicosatrienoic acid (DHET). The aim of this study is to investigate the functional effects of the genetic polymorphisms of CYP4F2*3, CYP2J2*7, sEH rs751141, CYP2C19*2 and *17, CYP2C9*2, *3, CYP4F3 rs3794987, CYP4A11 rs9333025 in preeclampsia and gestational hypertension in a Turkish population. A total of 155 healthy pregnant women as the control group, 58 preeclampsia and 110 gestational hypertention patients as the study group were included. Genetic analysis was performed using the polymerase chain reaction and restriction (RFLP) analysis. 20-HETE and DHET levels were measured using liquid chromatography-mass spectrometry (LC-MS). Significant differences were found in the allele frequency distributions of CYP2J2*7, CYP2C19*2 and *17, CYP4F3 rs3794987 genetic polymorphisms among control, preeclampsia and GH groups. DHET plasma levels were decreased in preeclampsia and GH groups compared to the control group; however, plasma 20-HETE levels were not changed. Our results may suggest that CYP2J2*7, CYP2C19*2, *17, CYP4F3 rs3794987 genetic polymorphisms may be useful as candidate biomarkers in the diagnosis and follow-up of treatment in patients with preeclampsia and gestational hypertension.