The association between two common mutations C677T and A1298C in human methylenetetrahydrofolate reductase gene and the risk for diabetic nephropathyin type II diabetic patients

Mutations of the methylenetetrahydrofolate reductase (MTHFR) gene have been shown to be associated with a predisposition to developing diabetic nephro pathy (DN) in specific populations. The frequency of two MTHFR mutations, a recently described mutation in the human MTHFR gene A1298C and C677T, whos e association with DN is already known, was determined in an Israeli Jewish population with type 2 diabetes mellitus (DM). Both A1298C and C677T are h ighly prevalent in the diabetic population with allele frequencies of 0.35 and 0.36, respectively. The genotype frequency and allele frequency for the se two polymorphisms in patients who are normoalbuminuric (n = 55) were com pared with those of patients who had either micro- or macroalbuminuria (n = 43). For both polymorphisms, there were no significant differences in eith er the genotype distribution or allele frequency in patients with or withou t DN. However, in patients with serum folate <15.4 nmol/L, there was a grea ter incidence of DN in those patients who were homozygous or heterozygous f or the C677T mutation. For the A1298C mutation, there is evidence suggestin g that the homozygous state may be protective in patients with low-normal s erum folate. Folate supplementation in diabetic patients with the C677T mut ation and low-normal serum folate may prevent the onset or retard the progr ession of DN.