Methylenetetrahydrofolate Reductase (Mthfr C677t) Gene Polymorphism Effect on Development of Diabetic Nephropathy in Egyptien Patients with Type 2 Diabetes Mellitus

Introduction: Genetic predisposition has been implicated in diabetic nephropathy (DN). Methylenetetrahydrofolate reductase (MTHFR) is a regulatory enzyme of homocysteine metabolism. The C677T variant of the methylenetetrahydrofolate reductase (MTHFR) gene may play a role in the development of not only vascular disease but also diabetic microangiopathies. In this study, we examined the distribution of the MTHFR genotypes and the association between the C677T variant and diabetic nephropathy. METHODS: 50 type 2 diabetes mellitus patients classified into 2 groups according to presence or absence of nephropathy as measured by urinary albumin /creatinine ratio into 2 groups, 27 patients without nephropathy and 23 with nephropathy and 20 controls were recruited in the study. Fasting blood glucose, HbA1C and serum creatinine were measured. Plasma total homocysteine level was measured using chemilumenecent assay. MTHFR genetic C677T polymorphism was determined with PCR-restriction fragment length polymorphisms (RFLP). RESULTS: The frequency of MTHFR TT genotype and CT heterogenetic type and allele T(30.4\%, 43.5\%, 52\%) was significantly higher in type 2 diabetes mellitus with diabetic nephropathy group than those without nephropathy (7.4\%, 25.9\%, 20\%) or normal controls (10\%, 25\%, 22\%). However, there was no significant difference of MTHFR genotype and allele frequency between type 2 diabetes mellitus without nephropathy and normal controls (chi(2) 0.1, p value < 0.05). The presence of T allele appeared to have a stronger association with the development of diabetic nephropathy. The odds ratio was 5.7 and the 95\% confidence interval was 1.7-19.3. Moreover, plasma homocysteine levels were markedly higher in patients with TT or CT genotype than those in patients with CC genotype. CONCLUSIONS: Our findings suggest that the C677T mutation in the MTHFR gene predisposes type 2 diabetes patients to the development of diabetic nephropathy. The T allele of this mutation presumably acting by elevating homocysteine levels and seems to be associated with a faster progression of nephropathy to end-stage renal failure. {[}Samar M. Sharaf, Heba H. Gawish Enas M. Elsherbiny. Methylenetetrahydrofolate Reductase (Mthfr C677t) Gene Polymorphism Effect on Development Of Diabetic Nephropathy in Egyptien Patients with Type 2 Diabetes Mellitus. Life Sci J 2012; 9(2): 874-880].