title: Significance of H63D homozygosity in a Basque population with hemochromatosis.
abstract: BACKGROUND
  The significance of H63D homozygosity remains uncertain, although it is associated with a tendency for patients to develop iron overload.
  
  
  OBJECTIVE
  To study the prevalence of homozygotic H63D mutation in patients with phenotypic hemochromatosis (PH) and to compare the results with those of the general population and with patients with porphyria cutanea tarda (PCT) in the Basque Country, Spain. A secondary aim was to evaluate the differences in phenotypic expression and liver injury according to different genotypes in the PH cohort.
  
  
  METHODS
  Mutations of the HFE gene were obtained by polymerase chain reaction (PCR). Forty consecutive patients diagnosed with PH, 116 controls and 54 patients with PCT were included in the study. We performed liver biopsies, measured liver iron concentration (LIC), by atomic spectrophotometry, serum ferritin and transferrin saturation, and compared the histology according to the genotype.
  
  
  RESULTS
  The H63D homozygote mutation was identified in 7.76% of the control group, in 7.50% of the PH group, and in 11.11% of patients with PCT (P > 0.05). The C282Y/C282Y mutation was present in 50% of patients with PH, and LIC was identified in 15/20. The LIC in C282Y/C282Y patients was higher than in H63D/H63D patients (P = 0.26), while H63D homozygosis caused greater iron overload in PH patients than other genotypes. All the C282Y/C282Y genotype patients had elevated serum ferritin and transferrin saturation. The H63D homozygotes had high ferritin, but two out of three had normal transferrin saturation. Six of the eight patients with high-grade fibrosis and genetic study results were found to be C282Y/C282Y.
  
  
  CONCLUSIONS
  The prevalence of H63D mutation in patients with PH in our region does not differ from that of the general Basque population.
authors.affiliation: Gastroenterology Service, Mendaro Hospital, Barrio Mendarozabal, Basque Country, Spain. agustincastiella@yahoo.es
authors.forename: Agustin
authors.initials: A
authors.lastname: Castiella
authors.forename: Eva
authors.initials: E
authors.lastname: Zapata
authors.forename: Maria Dolores
authors.initials: MD
authors.lastname: de Juan
authors.forename: Pedro
authors.initials: P
authors.lastname: Otazua
authors.forename: Javier
authors.initials: J
authors.lastname: Fernandez
authors.forename: Leire
authors.initials: L
authors.lastname: Zubiaurre
authors.forename: Jose A
authors.initials: JA
authors.lastname: Arriola
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D005260:Female; D005293:Ferritins / Q000097:blood; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006432:Hemochromatosis / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007501:Iron / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017119:Porphyria Cutanea Tarda / Q000097:blood / Q000208:ethnology / Q000235:genetics; D012189:Retrospective Studies; D013030:Spain / Q000453:epidemiology; D013054:Spectrophotometry, Atomic; D014168:Transferrin / Q000378:metabolism; D044465:White People / Q000235:genetics*
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D014168:Transferrin; D005293:Ferritins; D007501:Iron