T-786C polymorphism in promoter of eNOS gene as genetic risk factor in patients with erectile dysfunction in Turkish population

Abstract

Objectives: To investigate the effect of 2 endothelial nitric oxide synthase gene polymorphisms, namely, variable number of 27-bp tandem repeats in intron 4 and T-786C in the promoter region, on the susceptibility to erectile dysfunction (ED) in Turkish population.

Methods: A total of 72 patients with ED (mean age 54.3 +/- 9.2 years) diagnosed by Doppler ultrasonography and 71 healthy controls (mean age 55.4 +/- 8.2 years) were analyzed. Genotypes were determined through polymerase chain reaction with or without restriction endonuclease digestions.

Results: Genotype distribution for CC genotype of T-786C polymorphism in promoter was significantly different between patients with ED and controls, the genotype frequency being 31.9% and 12.7%, respectively (P = .019). The univariate odds ratio (OR) associated with CC alleles revealed 3 times increased risk for ED (OR = 3.2; 95% confidence interval [CI], 1.4-7.6; P = .006). The risk also holds when excluding patients with hypertension and diabetes mellitus (P = .012, OR = 3.1; 95% CI, 1.2-7.7) as well as obesity (P = .05, OR = 4; 95% CI, 1.05-15.3). Patients with CC genotype of promoter present earlier symptoms of ED (51.7%) compared with controls (10.7%) (P <.001). No significant correlation was observed with variable number of tandem repeats in intron 4 and with the type of vascular insufficiency.

Conclusions: The CC genotype of T-786C polymorphism in the promoter of eNOS gene is associated with increased risk of ED in Turkish population. Earlier onset of ED with CC genotype suggests that CC allele is an independent risk factor for endothelial dysfunction in the absence of other risk factors (hypertension, diabetes mellitus, obesity). An impaired NO production because of CC alleles may account for pathophysiology of ED.