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01 February 2004

The C677T methylenetetrahydrofolate reductase gene mutation and nephropathy in type 2 diabetes mellitus

Piotr Książek, Anna Bednarek-Skublewska, Monika Buraczyńska

Med Sci Monit 2004; 10(2): BR47-51 :: ID: 11578

Abstract

Background:Diabetic nephropathy is a common cause of end-stage renal disease, responsible for about 35% of renal replacement therapy cases. The susceptibility to nephropathy is due to environmental and genetic factors and varies among individuals. Mutations of the methylenetetrahydrofolate reductase (MTHFR) gene have been shown to be associated with a predisposition to diabetic nephropathy in some populations.Material/Methods: The study population consisted of 326 patients with type 2 diabetes and 170 healthy control subjects. Genotyping for the C677T mutation in the MTHFR gene was performed using polymerase chain reaction (PCR) and gel analysis.Results: Allele and genotype frequencies did not differ significantly between the entire diabetic group and controls. There were statistically significant differences in genotype distribution between patients with nephropathy and those without. The diabetic nephropathy subgroup showed an increased frequency of the T allele as well as the TT genotype of the C677T mutation (p<0.05). The progression of renal failure to end-stage renal disease (ESRD) in dialyzed patients with diabetic nephropathy was influenced by this mutation. The mean time from diagnosis to the onset of ESRD was 3.6 years for patients with the TT genotype compared with 7.3 years for the CC genotype (p<0.01).
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 seems to be associated with a faster progression of nephropathy to end-stage renal failure.

Keywords: Alleles, Amino Acid Substitution, Diabetes Mellitus, Type 2 - enzymology, Diabetes Mellitus, Type 2 - genetics, Diabetic Nephropathies - enzymology, Diabetic Nephropathies - genetics, Gene Frequency, Genetic Predisposition to Disease, Genotype, Methylenetetrahydrofolate Reductase (NADPH2) - genetics, Mutation - physiology, Alleles, Amino Acid Substitution, Diabetes Mellitus, Type 2 - genetics, Diabetic Nephropathies - genetics, Gene Frequency, Genetic Predisposition to Disease, Genotype, Methylenetetrahydrofolate Reductase (NADPH2) - genetics, Mutation - physiology

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