The role of HFE mutations on iron metabolism in beta-thalassemia carriers.
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.
Martins
Rute
R
Centro de Genética Humana, Instituto Nacional de Saúde Dr Ricardo Jorge, Av. Padre Cruz, 1649-016, Lisbon, Portugal.
Picanço
Isabel
I
Centro de Genética Humana, Instituto Nacional de Saúde Dr Ricardo Jorge, Av. Padre Cruz, 1649-016, Lisbon, Portugal.
Fonseca
Aidil
A
Centro de Biopatologia, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisbon, Portugal.
Ferreira
Lídia
L
Centro de Biopatologia, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisbon, Portugal.
Rodrigues
Odete
O
Centro de Biopatologia, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisbon, Portugal.
Coelho
Marília
M
Centro de Biopatologia, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisbon, Portugal.
Seixas
Teresa
T
Centro de Biopatologia, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisbon, Portugal.
Miranda
Armandina
A
Centro de Biopatologia, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisbon, Portugal.
Nunes
Baltazar
B
Observatório Nacional de Saúde, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisbon, Portugal.
Costa
Luciana
L
Centro de Biopatologia, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisbon, Portugal.
Romão
Luísa
L
Centro de Genética Humana, Instituto Nacional de Saúde Dr Ricardo Jorge, Av. Padre Cruz, 1649-016, Lisbon, Portugal.
Faustino
Paula
P
Centro de Genética Humana, Instituto Nacional de Saúde Dr Ricardo Jorge, Av. Padre Cruz, 1649-016, Lisbon, Portugal. paula.faustino@insa.min-saude.pt.
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
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D014168:Transferrin; D007501:Iron