Article

The role of hemochromatosis C282Y and H63D gene mutations in type 2 diabetes: findings from the Rotterdam Study and meta-analysis.

Diabetes Care (Impact Factor: 8.57). 12/2002; 25(11):2112-3. DOI: 10.2337/diacare.25.11.2112-a
Source: PubMed

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    ABSTRACT: The hemochromatosis gene (HFE) has been involved in the etiology of type 2 diabetes mellitus and investigated in numerous epidemiologic studies. The current meta-analysis was conducted to evaluate the gene-disease association in relevant studies. Electronic literature search was performed on June 18, 2011, from databases of PubMed/MEDLINE, EMBASE, and HuGE Navigator. Articles were inspected by 2 authors independently, and data were extracted by identical extraction form. A total of 5,528 type 2 diabetes cases and 6,920 controls in relation to HFE polymorphisms (a cysteine to tyrosine substitution at amino acid position 282 (C282Y) and a histidine to aspartate substitution at amino acid position 63 (H63D)) were included in the meta-analysis (1997-2011). A fixed- or random-effect model was used to calculate the pooled odds ratios based on the results from the heterogeneity tests. An increased odds ratio for type 2 diabetes mellitus was observed in persons carrying a D allele at the H63D polymorphism compared with those with an H allele (odds ratio (OR) = 1.21, 95% confidence interval (CI): 1.03, 1.41; P = 0.02). Moreover, carriers of a D allele had a modestly increased risk compared with persons with the wild genotype (OR = 1.12, 95% CI: 1.00, 1.25; P = 0.04). The C282Y variant was not significantly associated with diabetes risk. In summary, persons with a D allele may have a moderately increased risk of type 2 diabetes mellitus.
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    ABSTRACT: Les 2 atteintes endocriniennes fréquentes de l'hémochromatose sont le diabète sucré et l'hypogonadisme hypogonadotrophique. Les autres endocrinopathies sont très rares, surtout décrites dans les surcharges en fer post-tranfusionnelles plus graves et plus précoces. La présence de ces complications endocrines chez un patient témoigne d'une hémochromatose déjà évoluée souvent associée à une cirrhose. Compte tenu de la faible fréquence des mutations HFE chez les diabétiques de type 2, faire une recherche génétique systématique dans cette population ne paraît pas raisonnable. Il est recommandé de rechercher une surcharge ferrique chez un sujet ayant un diabète de type 2 atypique (par exemple sans surpoids), en présence d'un hypogonadisme, d'une pigmentation évocatrice ou d'une cirrhose. Les saignées jouent un rôle important dans la prise en charge des complications endocrines des hémochromatoses, d'autant plus que le diagnostic a été fait précocement. Devant tout hypogonadisme hypogonadotrophique, il faut évoquer la possibilité d'une hémochromatose primitive.
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