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 beta 3 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 center dot 10(-4) and p = 3.2 center dot 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.