Role of hemochromatosis C282Y and H63D mutations in HFE gene in development of type 2 diabetes and diabetic nephropathy

OBJECTIVE - In patients with clinical hemochromatosis, the frequency of dia betes 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. Th ere are also some reports that suggest that iron overload might cause diabe tic nephropathy. RESEARCH DESIGN AND METHODS - We performed an association study to assess t he role of the C282Y and H63D mutations in the HFE gene as a risk factor fo r type 2 diabetes and diabetic nephropathy. Altogether, 563 patients with t ype 2 diabetes were included in the study. In the analyzed group, 108 patie nts had overt proteinuria, 154 had microalbuminuria, and 301 had normoalbum inuria. Among the patients with normoalbuminuria, only those with known dia betes duration greater than or equal to 10 years were considered normoalbum inuric (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 pol ymerase chain reaction-based protocol. RESULTS - There was an increased frequency of 282Y allele carriers among pa tients 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 a mong 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 nephrop athy in type 2 diabetic patients. We also confirmed previous observations t hat the frequency of the 282Y mutation was higher in patients with type 2 d iabetes than it was in the general population of healthy subjects.