(Journal Article): Role of hemochromatosis C282Y and H63D mutations in HFE gene in development of type 2 diabetes and diabetic nephropathy
 
Moczulski DK, Grzeszczak W, Gawlik B (Department of Internal Medicine and Diabetes, Silesian School of Medicine, Zabrze, Poland, kchwdiab@mail.slam.katowice.pl )
 
IN: Diabetes Care 2001; 24(7):1187-91
Impact Factor(s) of Diabetes Care: 7.071 (2004), 7.501 (2003), 5.477 (2002), 5.404 (2001)

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ABSTRACT: OBJECTIVE: In patients with clinical hemochromatosis, the frequency of diabetes ranges from 20 to 50%, and the heterozygosity for the C282Y mutation in the HFE gene might be associated with an increased risk for diabetes. There are also some reports that suggest that iron overload might cause diabetic nephropathy. RESEARCH DESIGN AND METHODS: We performed an association study to assess the role of the C282Y and H63D mutations in the HFE gene as a risk factor for type 2 diabetes and diabetic nephropathy. Altogether, 563 patients with type 2 diabetes were included in the study. In the analyzed group, 108 patients had overt proteinuria, 154 had microalbuminuria, and 301 had normoalbuminuria. Among the patients with normoalbuminuria, only those with known diabetes duration > or = 10 years were considered normoalbuminuric (n = 162). A total of 196 unrelated healthy subjects were used as a control group. All subjects were genotyped for C282Y and H63D using the polymerase chain reaction-based protocol. RESULTS: There was an increased frequency of 282Y allele carriers among patients with type 2 diabetes versus healthy control subjects (OR 5.3, 95% CI 1.6-17.3). We observed an increased frequency of the 63D allele carriers among patients with diabetic nephropathy (1.8, 1.2-2.8). CONCLUSIONS: In conclusion, our study is the first to indicate that being a carrier of the H63D hemochromatosis mutation is a risk factor for nephropathy in type 2 diabetic patients. We also confirmed previous observations that the frequency of the 282Y mutation was higher in patients with type 2 diabetes than it was in the general population of healthy subjects.

TYPE OF PUBLICATION: Original article

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