73 Genetic variability in oxidative stress-related gene polymorphisms (GSTM1, GSTT1, NOS3 and MTHFR) in preeclampsia and future cardiovascular risk

Abstract

Introduction Preeclampsia (PE) may affect the risk for future cardiovascular disease. Oxidative stress and genetic polymorphisms associated to this pathway may modulate that risk through the antioxidant and anti-inflammatory differential effects of their genotypes. Objectives To study the association between oxidative stress-related gene polymorphisms (GSTM1, GSTT1, NOS3 and MTHFR) with the risk for preeclampsia and future cardiovascular risk. Methods We evaluated 222 women, aged 35.11±5.51years, 124 (55.9%) with normal blood pressure in pregnancy and 98 (44.1%) with preeclampsia (PE). In a sub-sample of these, we also evaluated in a prospective study, 88 (62.9%) women that had previous PE 2 to 16 years ago. The GSTM1, GSTT1 and NOS3 a/b polymorphisms were determined by PCR and MTHFR C677T was determined by PCR-RFLP. In the prospective cohort, we studied demographic, anthropometric, and haemodynamic biomarkers such as C-reactive protein, myeloperoxidase, and nitric oxide metabolites (total and nitrites), and others associated with liver function (AST and ALT) and lipid profile (total LDL and cholesterol HDL, non-HDL and apolipoproteins A and B). For statistical analysis Student t -test and binary regression logistic were used. P Results We found lower PE risk associated to GSTT1 null (OR=0.48; 95% CI=0.25–0.96; P =0.038) and an increased PE risk associated to MTHFR C carriers (OR=4.18; 95% CI=1.36–12.81; P =0.012). The latter was also significantly associated to PE risk in a multivariate analysis (OR=4.43; 95% CI=1.41–3.14; P =0.011). The two-way combination of GSTT1 non-null and MTHFR C carriers, adjusted for age, resulted in almost 3-fold increased PE risk (OR=2.74; 95% CI=1.20–6.69; P =0.018). In the prospective cohort, for the GSTT1 non-null and MTHFR C carriers risk genotypes, we found that PE women that developed later hypertension, presented significantly higher levels of LDL in relation to those that became normotensive (138.53±45.20 versus 104.16±30.81; P =0.025). NOS3 and GSTM1 polymorphisms were not associated to risk for PE. Conclusions The present study indicates that oxidative stress-related gene polymorphisms, namely, the association of GSTT1 non-null and MTHFR C carriers genotypes may be involved in susceptibility for preeclampsia. For this risk genetic model and according with the previously history of PE, these women may be more susceptible to future cardiovascular risk in premenopausal.