Comprehensive insight into functional interaction between GNB3 C825T and eNOS T-786C, G894T gene polymorphisms and association with susceptibility to diabetic erectile dysfunction.

BACKGROUND: No study has assessed the possible involvement of endothelial nitric oxide synthase (eNOS) T-786C and G894T and G-protein β3 subunit (GNB3) C825T polymorphisms with susceptibility to diabetic vasculogenic erectile dysfunction (VED) in North African subjects.

OBJECTIVES: Our aim was to evaluate the interaction and association between these gene polymorphisms and this disorder.

MATERIALS AND METHODS: A total of 164 type 2 diabetes patients with VED diagnosed with penile color Doppler ultrasonography and 148 age-matched healthy volunteers were genotyped for the rs1799983 (G894T) and rs2070744 (T-786C) of the eNOS gene and the rs5443 (C825T) of the GNB3 gene using the PCR-RFLP method.

RESULTS: A significant association of the eNOS G894T (p = 0.005) and T-786C (p = 0.02) with altered susceptibility to VED was observed. The risk also holds for the G894T and T-786C eNOS gene polymorphisms when excluding patients with dyslipidemia and cardiovascular diseases (p = 1.7·10-4 and p = 3.2·10-5 , respectively). The univariate odds ratio associated with CC alleles of the eNOS T-786C revealed a four times increased risk for VED (OR = 4.04; 95% CI = 1.53-10.67; p = 0.006). VED risk was also associated with the G894T variant under dominant model (p = 0.002) and the T-786C variant under recessive model (p = 0.004). Furthermore, the concomitant presence of the combined genotypes of the 894T and 786T strongly affected the predisposition to VED (p = 0.007).

DISCUSSION AND CONCLUSION: Our study gave a comprehensive insight into functional interaction between GNB3 and eNOS gene polymorphisms and suggests that the eNOS G894T and T-786C variants are strong predisposing factors of VED susceptibility within men with type 2 diabetes.