Background: Diabetic nephropathy (DN) is a chronic microangiopathic complication of type 2 diabetes mellitus (DM).Vascular endothelial dysfunction resulting from impaired nitric oxide synthase (NOS) activity in the vascular endothelial cells has been suggested as playing an important role in the pathogenesis of diabetic nephropathy (DN). Endothelial nitric oxide synthase (E-NOS) gene G894T polymorphism has been reported to be associated with endothelial dysfunction leading to DN. Our objective was to evaluate the association of G894T polymorphism of eNOS gene with the risk of DN among type 2 diabetic Saudi patients.
Methods: One hundred and twenty subjects were included in this study. They were divided into three groups. Group I, 40 controls. Group II, 40 type 2 diabetic patients without nephropathy. Group III, 40 type2 diabetic patients with nephropathy. Endothelial nitric oxide synthase (eNOS) G894Tpolymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Plasma nitric oxide (NO) levels were estimated.
Results: E-NOS genotype frequency showed non-significant differences among the all studied groups (p > 0.05). Both diabetic groups had significantly higher plasma nitrate levels than in controls with a significant increase in group III than in group II patients (all p < 0.0001). E NOS 894TT genotype was associated with higher plasma nitrate levels in all groups.
Conclusion: E-NOS gene SNP is not considered as genetic risk factor for DN among type 2 diabetic Saudi patients. The higher plasma levels of nitrates as a marker of oxidative stress in diabetic patients with nephropathy suggest the possible role of oxidative stress but not e-NOS gene SNP in pathogenesis of the DN.
Keywords: Diabetic nephropathy; E-NOS gene G894T polymorphism; Endothelial nitric oxide synthase (e-NOS) enzyme; Microangiopathy in type 2 diabetes mellitus (DM).