Endothelial nitric oxide synthase polymorphisms and erectile dysfunction: a meta-analysis

Abstract

Introduction: Erectile dysfunction (ED) is a common disorder noted for affecting quality of life. Several studies have reported the influence of endothelial nitric oxide synthase (eNOS) polymorphisms on ED susceptibility. However, results of association studies with individually low statistical power are conflicting.

Aim: Our study aimed to carry out a meta-analysis estimating the association between eNOS variants and the risk of ED.

Methods: Studies regarding the association between eNOS polymorphisms and ED were searched in Medline and Embase databases. The relevant studies that met the inclusion criteria were eligible for the analysis.

Main outcome measures: Five genetic models and a generalized odds ratio (OR(G) ) were used to estimate the association between eNOS G894T and variable number of 27-bp tandem repeats in intron 4 (4 VNTR) and the risk of ED.

Results: Nine articles were included in our meta-analysis. Overall, significant association between the 894T variant and an increased risk of ED was derived for all genetic contrasts except for the recessive model (allele contrast: OR = 1.64, 95% confidence interval [CI]: 1.03-2.60). The meta-analysis based on the OR(G) also produced significant results: OR(G) = 1.64, 95% CI: 1.03-2.61. Significant heterogeneity and publication bias were detected. The cumulative meta-analysis showed the OR increased from 2003 to 2009 and then declined in 2010. Instability in the relative change of OR was observed. Regarding 4 VNTR and its association with ED, the overall analysis showed a lack of significant association (OR = 0.96, 95% CI: 0.72-1.28). No evidence for heterogeneity among studies was observed. Subgroup analysis by ethnicity and recruitment strategy also yielded nonsignificant results.

Conclusion: The result supports that G894T variant is associated with an increase in the risk of ED. No evidence for a significant association between 4VNTR and ED is observed. The results of the present meta-analysis should be interpreted with caution. Further confirmation in large and well-designed studies is needed.