title: The significance of haemochromatosis gene mutations in the general population: implications for screening.
abstract: BACKGROUND
  Haemochromatosis is associated with mutations in the HFE gene but the significance of these mutations in the general population is unknown.
  
  
  OBJECTIVE
  To determine the frequency of HFE gene mutations in the general population, their effect on serum iron indexes, and their role in screening for haemochromatosis.
  
  
  METHODS
  Deoxyribonucleic acid (DNA) from 1064 randomly selected subjects was analysed for the C282Y and H63D mutations in the HFE gene. Serum iron, transferrin saturation, and ferritin were measured and individuals with increased iron indexes were investigated to confirm or exclude a clinical diagnosis of haemochromatosis.
  
  
  RESULTS
  Mutations were identified in 409 individuals (38.4%) with heterozygote (carrier) frequencies of 13.2% and 24.3% for the C282Y and H63D mutations respectively. Heterozygosity for either mutation significantly increased serum iron and transferrin saturation but despite a similar trend for ferritin, this was only significant for C282Y homozygotes. Five individuals (0.47%) were homozygous for the C282Y mutation, three of whom had haemochromatosis confirmed by liver biopsy (0.28%). The other two C282Y homozygotes would not have been detected by phenotypic screening alone.
  
  
  CONCLUSIONS
  HFE mutations are present in 38.4% of the population, affect serum iron indexes, and are important determinants of iron status. The population frequency of genetically defined haemochromatosis (C282Y homozygosity) is approximately one in 200 and is higher than the prevalence of clinically apparent haemochromatosis.
authors.affiliation: Department of Medicine, Christchurch Hospital, Christchurch, New Zealand.
authors.forename: M J
authors.initials: MJ
authors.lastname: Burt
authors.forename: P M
authors.initials: PM
authors.lastname: George
authors.forename: J D
authors.initials: JD
authors.lastname: Upton
authors.forename: J A
authors.initials: JA
authors.lastname: Collett
authors.forename: C M
authors.initials: CM
authors.lastname: Frampton
authors.forename: T M
authors.initials: TM
authors.lastname: Chapman
authors.forename: T A
authors.initials: TA
authors.lastname: Walmsley
authors.forename: B A
authors.initials: BA
authors.lastname: Chapman
mesh_terms: D005260:Female; D005820:Genetic Testing / Q000379:methods*; D005838:Genotype; D006432:Hemochromatosis / Q000097:blood / Q000235:genetics* / Q000517:prevention & control; D006720:Homozygote; D006801:Humans; D007501:Iron / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009520:New Zealand / Q000453:epidemiology; D014168:Transferrin / Q000378:metabolism
chemical_list: D014168:Transferrin; D007501:Iron