Association of G894T polymorphism in endothelial nitric oxide synthase gene with the risk of ischemic stroke: A meta-analysis

Abstract

Findings of a previous meta-analysis demonstrated no association between G894T polymorphism in endothelial nitric oxide synthase (eNOS) gene and ischemic stroke. Results of other studies have also been inconsistent. Updated meta-analysis was performed to assess the association between the eNOS gene G894T (rs1799983) polymorphism and the risk of ischemic stroke. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) from fixed and random effects models were calculated. Heterogeneity in the studies was evaluated using the I². Meta-regression and the 'leave-one-out' sensitive analysis were used to examine the potential sources of between-study heterogeneity. Publication bias was estimated using the Egger's test. Data were available for 6,607 cases and 6,947 controls from 22 studies. Studies deviating from the Hardy-Weinberg equilibrium (HWE) in the controls and the key contributors to between-study heterogeneity were excluded. Significant associations between eNOS gene G894T polymorphism and the risk of ischemic stroke were observed in the dominant (OR 1.249; 95% CI, 1.145-1.361), the recessive (OR 1.255; 95% CI, 1.082-1.456) and the codominant models (OR 1.195; 95% CI, 1.115-1.281). Moreover, in the subgroup analysis based on the region (Asia and Europe), significant associations were observed between the dominant and codominant genetic models but not in the recessive model. The results of our meta-analysis suggested that eNOS gene G894T polymorphism was associated with the increased risk of ischemic stroke, and that the T allele may be an important risk factor for ischemic stroke. However, further studies are required to confirm this result.

Keywords: G894T; endothelial nitric oxide synthase gene; gene polymorphism; ischemic stroke; meta-analysis.

Figure 1.

Forest plots of correlation between eNOS gene G894T polymorphism and ischemic stroke risk in dominant (TT+GT vs. GG) model following hte exclusion of studies that deviated from Hardy-Weinberg equilibrium (HWE) in controls, a study in Africa and ‘leave-one-out’ sensitive analysis. White diamond, the pooled OR. Black squares, the OR in each study, with square sizes that are inversely proportional to the standard error of the OR. Horizontal lines represent 95% CIs. OR, odds ratio.

Figure 2.

Analysis of influence of meta-analysis estimates, given named study is omitted is shown, i.e., the individual study on the pooled estimate in the dominant model (TT+GT vs. GG) of the eNOS gene G894T polymorphism, following the exclusion of studies deviating from HWE in the controls and ‘leave one-out’ sensitive analysis. Open circle, the pooled OR, given named study is omitted. Horizontal lines represent the 95% CIs. OR, odds ratio.