The Association between Two Common Mutations C677T and A1298C in Human Methylenetetrahydrofolate Reductase Gene and the Risk for Diabetic Nephropathy in Type II Diabetic Patients

Abstract

Mutations of the methylenetetrahydrofolate reductase (MTHFR) gene have been shown to be associated with a predisposition to developing diabetic nephropathy (DN) in specific populations. The frequency of two MTHFR mutations, a recently described mutation in the human MTHFR gene A1298C and C677T, whose association with DN is already known, was determined in an Israeli Jewish population with type 2 diabetes mellitus (DM). Both A1298C and C677T are highly prevalent in the diabetic population with allele frequencies of 0.35 and 0.36, respectively. The genotype frequency and allele frequency for these two polymorphisms in patients who are normoalbuminuric (n = 55) were compared with those of patients who had either micro- or macroalbuminuria (n = 43). For both polymorphisms, there were no significant differences in either the genotype distribution or allele frequency in patients with or without DN. However, in patients with serum folate <15.4 nmol/L, there was a greater incidence of DN in those patients who were homozygous or heterozygous for the C677T mutation. For the A1298C mutation, there is evidence suggesting that the homozygous state may be protective in patients with low-normal serum folate. Folate supplementation in diabetic patients with the C677T mutation and low-normal serum folate may prevent the onset or retard the progression of DN.

Endothelial nitric oxide synthase gene polymorphisms and diabetic nephropathy: A HuGE review and meta-analysis

“…However, the etiology of DN is multifactorial and involves both environmental and genetic factors. 18 A familial clustering of DN indicated that a genetic predisposition is implicated in the pathogenesis of DN in both types of diabetes. 19 -23 Nevertheless, the genetic component of the pathophysiologic process of DN has not yet been deciphered.…”

Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and susceptibility to diabetic nephropathy in Chinese type 2 diabetic patients: a meta-analysis

“…11 It was reported that elevated levels of plasma homocysteine was associated with diabetic nephropathy. 12,13 Thus, MTHFR C677T gene polymorphism associated with a predisposition to increased plasma homocysteine levels may present a genetic risk factor for DN.…”

Methylene Tetrahydrofolate Reductase C677T Mutation and Left Ventricular Hypertrophy in Turkish Patients with Type II Diabetes Mellitus

“…Their results differed (Neugebauer, 1998;Fujita et al, 1999;Abdella, 2000;Shpichinetsky et al, 2000;Ambrosch et al, 2001;Agullo-Ortuno et al, 2002;de Luis et al, 2002). In the previous study, Agullo-Ortuno et al (2002) studied the concentration of Hcy in the plasma of a group of type 1 and type 2 DM patients and took into account whether hyperhomocysteinemia was related to complications of the disease, such as macroangiopathy, nephropathy, retinopathy, and neuropathy.…”