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Nephrol Dial Transplant (2003) 18: 1535-1540
© 2003 European Renal Association-European Dialysis and Transplant Association

Effects of the C677T and A1298C polymorphisms of the MTHFR gene on the genetic predisposition for diabetic nephropathy

Dariusz Moczulski, Hanna Fojcik, Ewa Zukowska-Szczechowska, Ilona Szydlowska and Wladyslaw Grzeszczak

Department of Internal Medicine, Diabetology and Nephrology, Silesian School of Medicine, Zabrze, Poland

Correspondence and offprint request to: Hanna Fojcik, Department of Internal Medicine, Diabetology and Nephrology, Silesian School of Medicine, Zabrze, Poland. Email: hfojcik{at}poczta.onet.pl

Background. Methylenetetrahydrofolate reductase (MTHFR) is a regulatory enzyme of homocysteine metabolism. The C677T polymorphism of the MTHFR gene has been reported to be associated with elevated plasma homocysteine in patients with low folic acid intake. A recently reported second common polymorphism, A1298C, may increase homocysteine, but only in individuals carrying the T677 allele. This study aimed to investigate the influence of the C677T and A1298C polymorphisms of the MTHFR gene on the development of diabetic nephropathy in Caucasian patients with type 2 diabetes.

Methods. We genotyped 429 type 2 diabetic patients for the C677T and A1298C polymorphisms using standard PCR-based protocols, and divided them into three groups based on renal status: 159 patients with normoalbuminuria, 149 with microalbuminuria, and 121 with persistent proteinuria and chronic renal failure (CRF). The C677T and A1298C genotype frequencies were compared among the three groups.

Results. Although the frequencies of the CT and TT genotypes of the C677T polymorphism tended to increase with each stage of diabetic nephropathy (53, 56 and 63% in normoalbuminuria, microalbuminuria and proteinuria/CRF, respectively), these differences were not significant. When male and female patients were analysed separately, the effect was seen only in males. The CT + TT genotype was present in 46% of male patients with normoalbuminuria, in 57% with microalbuminuria and in 68% with proteinuria/CRF (OR = 2.46; 95% CI 1.13–5.38). There were no differ-ences in the A1298C polymorphism among the three groups.

Conclusions. These findings indicate that the C677T polymorphism is a risk factor for diabetic nephrop-athy in male patients with type 2 diabetes.

Keywords: diabetic nephropathy; genetic susceptibility; homocysteine; MTHFR; type 2 diabetes mellitus


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