Endothelial nitric oxide synthase gene polymorphisms and risk of erectile dysfunction: An updated meta-analysis of genetic association studies

Endothelial nitric oxide synthase (eNOS) polymorphisms have been implicated as risk factors for erectile dysfunction (ED), but the results of genetic association studies are inconclusive. We performed a meta-analysis of published studies investigating the association between ED and three eNOS polymorphisms, intron 4 VNTR, G894T and T786C in humans. The PubMed, Web of Science, CNKI and Google Scholar databases were searched for relevant studies published up to November 2017. Association studies with case-control design were included. For each study with genotype information we calculated odds ratios (OR) and 95% confidence intervals (CI). The search identified 13 eligible studies. The G894T and T786C polymorphisms showed a significant association with ED risk in Caucasians (GT + TT versus GG for G894T: OR = 2.13, 95% CI = 1.08–4.19; CC versus CT + TT for T786C: OR = 3.29, 95% CI = 2.30–4.72) and Asians (GT + TT versus GG for G894T: OR = 2.08, 95% CI = 1.53–2.84; CC + CT versus TT for T786C: OR = 3.13, 95% CI = 1.35–7.25). In addition, the intron 4 VNTR polymorphism was associated with ED risk only among Caucasian subjects (aa versus bb + ab: OR = 2.38, 95% CI = 1.15–4.93). We found no evidence of publication bias. The robustness of overall analyses was ensured in sensitivity analyses excluding studies deviating from Hardy-Weinberg equilibrium. Our findings suggest that common genetic polymorphisms in the eNOS gene contribute to risk of ED, presumably by effects on eNOS activity and NO availability. •We performed a meta-analysis investigating the association between ED and three eNOS polymorphisms.•The G894T and T786C polymorphisms showed a significant association with ED risk in Caucasians.•The intron 4 VNTR polymorphism was associated with ED risk only among Caucasian subjects.•Common genetic polymorphisms in the eNOS gene contribute to risk of ED.