title: Prevalence of HFE C282Y and H63D in Jewish populations and clinical implications of H63D homozygosity.
abstract: The frequencies of C282Y and H63D mutations of the HFE gene vary between different populations. A previous study showed an unexpectedly high H63D frequency in Chuetas (a population of Jewish descent). The present study addressed the question of the distribution of these mutations in Jewish populations from different origins and studied the possible causes of the high H63D frequency in Chuetas. Moreover, to improve the understanding of the controversial relationship between H63D homozygosity and iron overload, a group of patients with altered iron metabolism were studied. The high frequency of H63D mutation in Chuetas is not due to a high prevalence of this mutation in Sephardic Jews. Jewish populations have low C282Y and moderate H63D frequencies, suggesting slight gene flow from their surrounding populations. In accordance with historical and demographic data, genetic drift is the most probable cause for the singular H63D frequency in Chuetas. Clinically, this study of H63D homozygotes supports the conclusion that this genotype must be taken into account, because it confers an increased risk of iron overload and therefore genetic susceptibility to developing hereditary hemochromatosis or to aggravating other diseases.
authors.affiliation: Laboratori de Genètica, Institut Universitari d'Investigacions en Ciències de la Salut (IUNICS) i Departament de Biologia, Universitat de les Illes Balears, Illes Balears, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Matas
authors.forename: P
authors.initials: P
authors.lastname: Guix
authors.forename: J A
authors.initials: JA
authors.lastname: Castro
authors.forename: M
authors.initials: M
authors.lastname: Parera
authors.forename: M M
authors.initials: MM
authors.lastname: Ramon
authors.forename: A
authors.initials: A
authors.lastname: Obrador
authors.forename: A
authors.initials: A
authors.lastname: Picornell
mesh_terms: D000483:Alleles; D005260:Female; D005787:Gene Frequency; D006432:Hemochromatosis / Q000235:genetics; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007585:Jews / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics*
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins