Methylenetetrahydrofolate reductase C677T gene polymorphism and diabetic nephropathy susceptibility in patients with type 2 diabetes mellitus

Abstract

Background Type 2 diabetes mellitus (T2DM) is becoming increasingly prevalent throughout the world. Diabetic nephropathy (DN) is one of the most serious microvascular complications of diabetes mellitus. The C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene has been reported to cause reduced MTHFR enzyme activity and impaired homocysteine metabolism, leading to hyperhomocysteinemia. Aim The aim of the study was to evaluate the role of MTHFR C677T gene polymorphism in the susceptibility to DN in type 2 diabetic patients. Patients and methods The study was conducted on 180 adult Egyptian participants (60 healthy controls, 60 patients with T2DM without nephropathy, and 60 patients with T2DM complicated with nephropathy). C677T genotypes were determined by PCR-RFLP analysis, and homocysteine levels were measured by enzyme-linked immunosorbent assay. Results The prevalence of polymorphic genotype of CT and TT and T allele was statistically significantly increased in diabetic patients than in controls (P<0.001). There was a statistically significant increase in polymorphic genotypes (CT and TT) and T allele in T2DM with nephropathy in comparison to T2DM without nephropathy group (P<0.001, 0.05, respectively). Serum homocysteine levels were significantly higher in patients with nephropathy than in patients without nephropathy or controls with P less than 0.001. The higher serum homocysteine level was observed with polymorphic genotypes TT and CT compared with CC genotypes (P<0.001). Conclusion The TT genotype and T allele of MTHFR C677T may represent a significant genetic molecular marker to predict the risk of DN in T2DM.