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

Abstract

Previous studies examining whether polymorphisms (G894T, 4b/a, and T786C) in the endothelial nitric oxide synthase (eNOS) gene are associated with ischemic stroke have yielded conflicting results. We performed a meta-analysis to investigate the potential association between these three eNOS gene polymorphisms and ischemic stroke risk. We searched databases until April 30, 2012 and used fixed or random effects models to estimate the pooled odds ratios (ORs). We analyzed 34 case-control data sets from 33 publications involving 5261/5823 cases/controls for G894T, 4295/4682 for 4b/a, and 2698/3254 for T786C polymorphisms. For Asian populations, all models showed significantly increased risk of ischemic stroke for the G894T (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 Bonferroni 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 T786C 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). Our comprehensive meta-analysis ascertains that the G894T, 4b/a, and T786C polymorphisms are associated with ischemic stroke risk in Asians. A possible contrasting role of the 4b/a polymorphism in ischemic stroke was indicated in white populations.