Serum Homocysteine and MTHFR C677T and A1298C gene polymorphisms in Type 2 Diabetic Patients with Nephropathy in Sector of Egyptian Population

Abstract

Homocysteine (Hcy) is an amino acid, which is a product of methionine demethylation and a precursor to cysteine biosynthesis. Elevations in plasma Hcy (homocysteinemia) are frequently found in increased risk of atherosclerotic, coronary artery disease (CAD), venous thrombosis and stroke. Hcy injuries the endothelium and may have a role in microvascular complication of type 2 diabetes mellitus (T2DM). Two common mutations in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene (MTHFR C677T and A1298C) result in elevated Hcy levels. The aim of the present study was to investigate the relationship between plasma Hcy levels and diabetic nephropathy (DN). Serum Hcy levels, MTHFR genotype, and a panel of variables were evaluated in a sample of 75 T2DM patients with DN, 55 patients without nephropathy and also 95 non-diabetic control Egyptian subjects. Its common genetic polymorphisms (MTHFR C677T and A1298C) were determined for these patients and control subjects together with their correlation with changes in Hcy levels. Biochemical variables (including 24 hours albuminuria, GFR and serum total Hcy, lipogram and HbA 1c beside blood urea and serum creatinine) and lifestyle characteristics were investigated. MTHFR genotype was studied by PCR-RFLP analysis, and total Hcy levels were measured by ELISA. The plasma Hcy levels were significantly higher in the diabetic nephropathy (19.8± 2.3 µmol/L) than uncomplicated type 2 diabetic patients (12.7± 2.1 µmol/L, P<0.05) and also, the control subjects (11.8±1.8µmol/L, P<0.05). There were no differences between uncomplicated diabetic patients and control subjects with respect to Hcy levels. C677T and T677T were highly prevalent among DN patients, with frequencies of 0.40 and 0.36 respectively. C677T, but not A1298C, SNP, is a risk factor for DN, presumably through elevating serum Hcy level.