Association of the T-786C, G894T and 4a/4b polymorphisms of the endothelial nitric oxide synthase gene with vasculogenic erectile dysfunction in Iranian subjects.

OBJECTIVE • To investigate the association of the T-786C, G894T and variable number of tandem repeats (VNTRs) in intron 4 (a/b) polymorphisms of the eNOS gene in Iranian subjects with vasculogenic erectile dysfunction (ED). PATIENTS AND METHODS • A total of 322 consecutive patients with vasculogenic ED were recruited. Patients with concomitant risk factors for ED were excluded. • Patients with ED were identified based on history-taking, detailed physical examination, serum biochemistry, sex hormone measurements, application of the International Index of Erectile Function (IIEF) questionnaire, and penile duplex Doppler ultrasonography after intracavernosal injection of 20 µ g prostaglandin E 1 . The control group comprised 318 age-matched healthy male volunteers. • Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism and the T-786C, G894T and VNTR intron 4 polymorphisms of the eNOS gene were determined. RESULTS • After multivariate regression analysis, significant differences were seen in the frequencies of genotypes and alleles of the two T-786C and G894T polymorphisms when patients with ED and normal controls were compared. • In a multiple logistic regression analysis, the odds ratio (OR) of increased ED was strongly associated with the -786C allele [adjusted OR = 3.12, 95% confidence interval (CI) = 2.28-4.25; P = 0.001] and the 894T allele (adjusted OR = 3.87, 95% CI = 2.53-4.87; P = 0.001). • The data showed a higher prevalence of the T-786C CC genotype (adjusted OR = 2.72, 95% CI = 1.88-3.65; P = 0.006), and the G894T GT (adjusted OR = 1.72, 95% CI 1.24-2.83; P = 0.037) and G894T TT genotypes (adjusted OR = 3.42, 95% CI 2.42-4.26; P = 0.001) in patients with ED than in the controls. CONCLUSIONS • The findings of the present study suggest that the eNOS T-786C and G894T polymorphisms are strong predictors of the predisposition to ED in addition to traditional risk factors, signifying a genetic influence for this multifactorial disease. • Further studies in different ethnic populations are needed to better elucidate the role of eNOS gene polymorphism in the pathogenesis of ED. [ABSTRACT FROM AUTHOR]