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25 February 2003

A search for association between hereditary hemochromatosis HFE gene mutations and type 2 diabetes mellitus in a Polish population.

Maciej T. Małecki, Tomasz Klupa, Małgorzata Waluś, Wojciech Czogała, Paul Greenlaw, Jacek Sieradzki

Med Sci Monit 2003; 9(2): BR91-95 :: ID: 4755

Abstract

BACKGROUND: Hereditary hemochromatosis (HH) is characterized by excess iron deposition. Two mutations in the HFE gene are associated with HH. Heterozygous carriers of HFE mutations are at higher risk of developing type 2 diabetes mellitus (T2DM). The aims of our project were to identify the frequency of C282Y and H63D mutations in a population from the Małopolska region of south-eastern Poland, and to search for an association of HFE mutations with T2DM. MATERIAL/METHODS: We included 391 individuals in this study: 222 T2DM patients and 169 controls. Genotypes were determined by electrophoresis of the DNA digestion products from SnaBI and DpnII, respectively. Differences in distributions between the groups were then analyzed by the chi-squared test. RESULTS: The frequency of wild/C282Y alleles was 98.2%/1.8% in T2DM patients and 96.7%/3.2% in controls (p=0.19). The frequency of wild/H63D alleles was 85.6%/14.4% and 88.8%/11.2% (p= 0.19), respectively. The distribution of genotypes was not statistically different. However, in stratified analyses based on age of T2DM onset and gender, we observed a higher prevalence of wild/H63D and H63D/H63D genotypes among T2DM patients diagnosed at > 49 years of age, the mean age for the entire group (p=0.018), and among male T2DM individuals (p=0.005) than in controls. CONCLUSIONS: The frequency of HH-associated mutations in this population from south-eastern Poland is similar to other Caucasians. We found no evidence for the association of the C282Y mutation with T2DM. The results do suggest, however, that the H63D mutation may play a role in the pathogenesis of late onset T2DM and in males in this Polish population.

Keywords: Adult, Case-Control Studies, Diabetes Mellitus, Type 2 - genetics, Gene Frequency, Genotype, Hemochromatosis - genetics, Histocompatibility Antigens Class I - genetics, Membrane Proteins - genetics, Point Mutation, Poland

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