An updated meta-analysis of endothelial nitric oxide synthase gene: three well-characterized polymorphisms with ischemic stroke.

Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene may influence the risk of ischemic stroke (IS), but the results are still debatable. A meta-analysis was performed to investigate the association between the eNOS gene polymorphisms in IS risk. Case-control studies on the association between the G894T, T-786C, and 4b/a polymorphisms and IS were searched up to July 2012, and the genotype frequencies in the control group were found to be consistent with the Hardy-Weinberg equilibrium (HWE). The effect summary odds ratio (OR) and 95% confidence intervals (CIs) were obtained. Meta-regression was used to explore the potential sources of heterogeneity. Funnel plots and Egger's test was used to estimate small study biases, and heterogeneity was assessed by chi-square-based Q-test and I(2) test. There were total 6537/6475 cases/controls for G894T, 3459/3951 cases/controls for 4b/a, and 2125/2673 cases/controls for T-786C polymorphism. For G894T and 4b/a, a significant association of 894T allele and 4a allele with increased risk of IS was found in Asians (TT+GT vs. GG: p<0.00001, OR=1.60, 95% CI=1.38-1.79, Pheterogeneity=0.11; aa+ba vs. bb: P<0.00001, OR=1.60, 95% CI=1.30-1.97, Pheterogeneity=0.02), but not in Caucasians (TT+GT vs. GG: P=0.60, OR=0.94, 95% CI=0.75-1.19, Pheterogeneity=0.002; aa+ba vs. bb: P=0.13, OR=0.81, 95% CI=0.62-1.06, Pheterogeneity=0.63). For T-786C polymorphism, there were no significant differences in genotype distribution between IS and control in Asians (CC+TC vs. TT: P=0.15, OR=1.14, 95% CI=0.95-1.37, Pheterogeneity=0.94) and in Caucasians (CC+TC vs. TT: P=0.72, OR=0.96, 95% CI=0.75-1.22, Pheterogeneity=0.53). This analysis provides strong evidence that the eNOS T-786C gene polymorphism is not associated with IS, the G894T and 4b/a polymorphisms might be associated with IS, at least in Asians.