Relationship between endothelial nitric oxide synthase gene polymorphisms and ischemic stroke: a meta‐analysis

Objectives Previous studies examining whether polymorphisms ( G 894T, 4b/a, and T 786C) in the endothelial nitric oxide synthase (e NOS ) gene are associated with ischemic stroke have yielded conflicting results. We performed a meta‐analysis to investigate the potential association between these three e NOS gene polymorphisms and ischemic stroke risk. Materials and methods We searched databases until April 30, 2012 and used fixed or random effects models to estimate the pooled odds ratios ( OR s). Results We analyzed 34 case–control data sets from 33 publications involving 5261/5823 cases/controls for G 894T, 4295/4682 for 4b/a, and 2698/3254 for T 786C polymorphisms. For A sian populations, all models showed significantly increased risk of ischemic stroke for the G 894T (dominant model: OR  = 1.58; 95% CI , 1.30–1.91; P  = 0.000) and 4b/a polymorphisms (dominant model: OR  = 1.46; 95% CI , 1.25–1.71; P  = 0.000), even after B onferroni correction (because 0.000 < 0.017). In white populations, the aa genotype seemed to be protective for ischemic stroke, as indicated by the recessive model ( OR  = 0.44; 95% CI , 0.22–0.87; P  = 0.019). In Asian populations, the T 786C polymorphism was significantly associated with ischemic stroke, as found using the dominant ( OR  = 1.17; 95% CI, 1.02–1.34; P  = 0.025) and additive models ( OR  = 1.18; 95% CI , 1.05–1.33; P  = 0.006). Conclusions Our comprehensive meta‐analysis ascertains that the G 894T, 4b/a, and T 786C polymorphisms are associated with ischemic stroke risk in A sians. A possible contrasting role of the 4b/a polymorphism in ischemic stroke was indicated in white populations.