title: HLA haplotypes associated with hemochromatosis mutations in the Spanish population.
abstract: BACKGROUND
  The present study is an analysis of the frequencies of HLA-A and -B antigens and HLA haplotypes in two groups of individuals homozygous for the two main HFE mutations (C282Y and H63D) and a group heterozygous for the S65C mutation.
  
  
  METHODS
  The study population includes: 1123 healthy individuals, 100 homozygous for the C282Y mutation, 138 homozygous for the H63D mutation and 17 heterozygous for the S65C mutation. HFE and HLA alleles were detected using DNA-based and microlymphocytotoxicity techniques respectively.
  
  
  RESULTS
  An expected significant association between C282Y and the HLA-A3/B7 haplotype was found, but other HLA haplotypes carrying the -A3 antigen were found: HLA-A3/B62 and HLA-A3/B44. Also, a significant association between H63D mutation and HLA-A29/B44 haplotype was found, and again other HLA haplotypes carrying the HLA-A29 antigen were also found: HLA-A29/B14 and HLA-A29/B62. In addition, the S65C mutation seems to be associated with a HLA haplotype carrying the HLA-A26 antigen.
  
  
  CONCLUSIONS
  These findings clearly suggest that HLA-A3/B7 and HLA-A29/B44 are the ancestral haplotypes from which the C282Y and H63D mutations originated, respectively. The frequencies of these mutations in different populations, their geographical distribution, and the degree of the statistical association to the ancestral haplotypes, suggest that the H63D mutation must have occurred earlier than the C282Y mutation.
authors.affiliation: Immunology, Hospital Universitario 12 de Octubre, Carretera de Andalucia, 28041, Madrid, Spain. arantzapacho@yahoo.es
authors.forename: Arantza
authors.initials: A
authors.lastname: Pacho
authors.forename: Esther
authors.initials: E
authors.lastname: Mancebo
authors.forename: Manuel J
authors.initials: MJ
authors.lastname: del Rey
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Castro
authors.forename: Desamparados
authors.initials: D
authors.lastname: Oliver
authors.forename: Miguel
authors.initials: M
authors.lastname: García-Berciano
authors.forename: Luis
authors.initials: L
authors.lastname: González
authors.forename: Pablo
authors.initials: P
authors.lastname: Morales
mesh_terms: D005787:Gene Frequency; D015234:HLA-A Antigens / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics*; D006239:Haplotypes; D006432:Hemochromatosis / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D013030:Spain
chemical_list: C103673:HFE protein, human; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins