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

Objectives: 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.

Materials and methods: We searched databases until April 30, 2012 and used fixed or random effects models to estimate the pooled odds ratios (ORs).

Results: 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).

Conclusions: 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.