title: The role of HFE mutations on iron metabolism in beta-thalassemia carriers.
abstract: Hereditary hemochromatosis (HH) is an autosomal recessive disorder of iron metabolism characterized by increased iron absorption and progressive storage resulting in organ damage. HFE gene mutations C282Y and H63D are responsible for the majority of HH cases. A third HFE mutation, S65C, has been associated with the development of a mild form of hemochromatosis. The beta-thalassemia trait is characterized by mild, ineffective erythropoiesis that can induce excess iron absorption and ultimately lead to iron overload. The aim of this study was to evaluate the effect of genetic markers (HFE mutations C282Y, H63D, and S65C) on the iron status of beta-thalassemia carriers. A total of 101 individuals heterozygous for beta-thalassemia and 101 normal control individuals were studied. The allelic frequencies of C282Y (1.5 versus 3.5%), H63D (15.3 versus 18.3%), and S65C (1.0 versus 1.5%) did not differ significantly between beta-thalassemia carriers and normal controls. Serum iron (P=0.029) and transferrin saturation (P=0.009) were increased in beta-thalassemia carriers heterozygous for H63D mutation. The number of subjects carrying C282Y or S65C mutations was too low to conclude their effect on the iron status. These results suggest that the beta-thalassemia trait tends to be aggravated with the coinheritance of H63D mutation, even when present in heterozygosity.
authors.affiliation: Centro de Genética Humana, Instituto Nacional de Saúde Dr Ricardo Jorge, Av. Padre Cruz, 1649-016, Lisbon, Portugal.
authors.forename: Rute
authors.initials: R
authors.lastname: Martins
authors.affiliation: Centro de Genética Humana, Instituto Nacional de Saúde Dr Ricardo Jorge, Av. Padre Cruz, 1649-016, Lisbon, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Picanço
authors.affiliation: Centro de Biopatologia, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisbon, Portugal.
authors.forename: Aidil
authors.initials: A
authors.lastname: Fonseca
authors.affiliation: Centro de Biopatologia, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisbon, Portugal.
authors.forename: Lídia
authors.initials: L
authors.lastname: Ferreira
authors.affiliation: Centro de Biopatologia, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisbon, Portugal.
authors.forename: Odete
authors.initials: O
authors.lastname: Rodrigues
authors.affiliation: Centro de Biopatologia, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisbon, Portugal.
authors.forename: Marília
authors.initials: M
authors.lastname: Coelho
authors.affiliation: Centro de Biopatologia, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisbon, Portugal.
authors.forename: Teresa
authors.initials: T
authors.lastname: Seixas
authors.affiliation: Centro de Biopatologia, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisbon, Portugal.
authors.forename: Armandina
authors.initials: A
authors.lastname: Miranda
authors.affiliation: Observatório Nacional de Saúde, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisbon, Portugal.
authors.forename: Baltazar
authors.initials: B
authors.lastname: Nunes
authors.affiliation: Centro de Biopatologia, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisbon, Portugal.
authors.forename: Luciana
authors.initials: L
authors.lastname: Costa
authors.affiliation: Centro de Genética Humana, Instituto Nacional de Saúde Dr Ricardo Jorge, Av. Padre Cruz, 1649-016, Lisbon, Portugal.
authors.forename: Luísa
authors.initials: L
authors.lastname: Romão
authors.affiliation: Centro de Genética Humana, Instituto Nacional de Saúde Dr Ricardo Jorge, Av. Padre Cruz, 1649-016, Lisbon, Portugal. paula.faustino@insa.min-saude.pt.
authors.forename: Paula
authors.initials: P
authors.lastname: Faustino
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006432:Hemochromatosis / Q000235:genetics*; D000071020:Hemochromatosis Protein; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000097:blood; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics; D014168:Transferrin / Q000032:analysis; D017086:beta-Thalassemia / Q000097:blood* / Q000235:genetics
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D014168:Transferrin; D007501:Iron