title: A high prevalence of HLA-H 845A mutations in hemochromatosis patients and the normal population in eastern England.
abstract: We have examined normal individuals and all the patients currently being treated for hemochromatosis at the Norfolk and Norwich hospital for mutations in the HLA-H gene. We found a gene frequency in 200 normal subjects for teh 845A (C282Y) allele of 0.085, corresponding to a carrier frequency of 17% which is among the highest reported anywhere in the world. The frequency for the less penetrant 187G (H63D) allele was 0.16 among 58 of the normal subjects, which corresponds to a carrier frequency of 32%. All 18 hemochromatosis patients were homozygous for the 845A allele which is not significantly different from other reports in our subset of 12 unrelated patients. These findings present a snapshot of a relatively stable population containing a predicted 3,500 individuals homozygous for the 845A allele but not diagnosed with hemochromatosis. This population will be an excellent model for studies on the penetrance of the 845A homozygous genotype and population screening.
authors.affiliation: Department of Molecular Genetics, Norfolk and Norwich Hospital, Brunswick Road, Norwich NR1 3SR, UK. gain@molgennn.demon.co.uk
authors.forename: G
authors.initials: G
authors.lastname: Willis
authors.forename: B A
authors.initials: BA
authors.lastname: Jennings
authors.forename: E
authors.initials: E
authors.lastname: Goodman
authors.forename: I W
authors.initials: IW
authors.lastname: Fellows
authors.forename: J Z
authors.initials: JZ
authors.lastname: Wimperis
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D004739:England; D005260:Female; D005787:Gene Frequency; D006680:HLA Antigens / Q000235:genetics*; D006432:Hemochromatosis / Q000235:genetics* / Q000276:immunology; D000071020:Hemochromatosis Protein; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008565:Membrane Proteins; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012016:Reference Values
chemical_list: C103673:HFE protein, human; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins