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

Andrology. 2018 Nov;6(6):865-873. doi: 10.1111/andr.12543. Epub 2018 Aug 12.

Abstract

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.

Keywords: GNB3; diabetes; eNOS; erectile dysfunction; gene polymorphisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Diabetic Angiopathies / diagnostic imaging
  • Diabetic Angiopathies / enzymology
  • Diabetic Angiopathies / genetics*
  • Diabetic Angiopathies / physiopathology
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Haplotypes
  • Heredity
  • Heterotrimeric GTP-Binding Proteins / genetics*
  • Humans
  • Impotence, Vasculogenic / diagnostic imaging
  • Impotence, Vasculogenic / enzymology
  • Impotence, Vasculogenic / genetics*
  • Impotence, Vasculogenic / physiopathology
  • Male
  • Middle Aged
  • Nitric Oxide Synthase Type III / genetics*
  • Penile Erection / genetics*
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Risk Assessment
  • Risk Factors
  • Tunisia
  • Ultrasonography, Doppler, Color

Substances

  • GNB3 protein, human
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III
  • Heterotrimeric GTP-Binding Proteins