Endothelial Nitric Oxide Synthase Gene Intron 4 Polymorphism in Type 2 Diabetes Mellitus

Introduction: Endothelial nitric oxide synthase (ecNOS) is a key regulator of vascular nitric oxide production. Polymorphism in intron 4 of the ecNOS gene is implicated in cardiovascular and renal diseases. We investigated a potential involvement of this polymorphism in the development of type 2 diabetes mellitus and its renal complications.

Methods: This preliminary study involved 410 individuals with type 2 diabetes and 330 healthy control subjects. From the diabetes group 178 patients had diabetic nephropathy. All subjects were genotyped for the ecNOS4 polymorphism by the polymerase chain reaction (PCR) followed by gel electrophoresis. Genotype and allele frequencies were compared between diabetes patients with and without nephropathy and the control group. All calculations were performed using the Statistical Package for the Social Sciences (SPSS, Inc., Chicago, IL, USA) for Windows 5.0. The chi-square test and Fisher’s exact test were used for case-control comparisons. The Kruskal-Wallis test was used for the comparison of subgroups of patients with diabetes.

Results: The analysis revealed that patients with diabetes, regardless of their nephropathy status, were significantly different in genotype distribution and 4a allele frequencies compared with controls (p < 0.05). The frequency of aa genotype was 8.2% in diabetic patients without nephropathy, 8.4% with those with nephropathy and 1.2% in controls. The 4a allele showed a significant effect on diabetic nephropathy, with odds ratio of 2.24 (95% confidence interval 1.12–3.40). There were no significant differences in the 4a allele frequency between the normotensive and hypertensive patients with diabetes.

Conclusion: Our results suggest that the ecNOS gene polymorphism can serve as a useful genetic marker of increased susceptibility to type 2 diabetes and its renal complications.