title: Analysis of HLA-A antigens and C282Y and H63D mutations of the HFE gene in Brazilian patients with hemochromatosis.
abstract: The hemochromatosis gene, HFE, is located on chromosome 6 in close proximity to the HLA-A locus. Most Caucasian patients with hereditary hemochromatosis (HH) are homozygous for HLA-A3 and for the C282Y mutation of the HFE gene, while a minority are compound heterozygotes for C282Y and H63D. The prevalence of these mutations in non-Caucasian patients with HH is lower than expected. The objective of the present study was to evaluate the frequencies of HLA-A antigens and the C282Y and H63D mutations of the HFE gene in Brazilian patients with HH and to compare clinical and laboratory profiles of C282Y-positive and -negative patients with HH. The frequencies of HLA-A and C282Y and H63D mutations were determined by PCR-based methods in 15 male patients (median age 44 (20-72) years) with HH. Eight patients (53%) were homozygous and one (7%) was heterozygous for the C282Y mutation. None had compound heterozygosity for C282Y and H63D mutations. All but three C282Y homozygotes were positive for HLA-A3 and three other patients without C282Y were shown to be either heterozygous (N = 2) or homozygous (N = 1) for HLA-A3. Patients homozygous for the C282Y mutation had higher ferritin levels and lower age at onset, but the difference was not significant. The presence of C282Y homozygosity in roughly half of the Brazilian patients with HH, together with the findings of HLA-A homozygosity in C282Y-negative subjects, suggest that other mutations in the HFE gene or in other genes involved in iron homeostasis might also be linked to HH in Brazil.
authors.affiliation: Hospital Português de Salvador, Salvador, BA, Brasil. plbbr@uol.com.br
authors.forename: P L
authors.initials: PL
authors.lastname: Bittencourt
authors.forename: S A
authors.initials: SA
authors.lastname: Palácios
authors.forename: C A
authors.initials: CA
authors.lastname: Couto
authors.forename: E L R
authors.initials: EL
authors.lastname: Cançado
authors.forename: F J
authors.initials: FJ
authors.lastname: Carrilho
authors.forename: A A
authors.initials: AA
authors.lastname: Laudanna
authors.forename: J
authors.initials: J
authors.lastname: Kalil
authors.forename: L C C
authors.initials: LC
authors.lastname: Gayotto
authors.forename: A C
authors.initials: AC
authors.lastname: Goldberg
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D019943:Amino Acid Substitution; D001483:Base Sequence; D001938:Brazil / Q000453:epidemiology; D005820:Genetic Testing; D006680:HLA Antigens / Q000235:genetics*; D015234:HLA-A Antigens / Q000235:genetics*; D006432:Hemochromatosis / Q000453:epidemiology / Q000235:genetics*; D000071020:Hemochromatosis Protein; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D015995:Prevalence
chemical_list: C103673:HFE protein, human; D006680:HLA Antigens; D015234:HLA-A Antigens; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins