title: HFE genotype in patients with hemochromatosis and other liver diseases.
abstract: BACKGROUND
  Hereditary hemochromatosis is a common inherited disorder of iron metabolism. The gene HFE, which contains two missense mutations (C282Y and H63D), was recently identified.
  
  
  OBJECTIVE
  To determine how HFE genotyping for the C282Y and H63D mutations contributes to the diagnosis of hemochromatosis and to determine the prevalence of HFE mutations in a group of patients with liver disease.
  
  
  METHODS
  Cross-sectional study.
  
  
  METHODS
  Academic medical center.
  
  
  METHODS
  66 patients with hereditary hemochromatosis and 132 referred patients with other liver diseases.
  
  
  METHODS
  At initial diagnosis, fasting transferrin saturation, ferritin level, routine chemistry panel, and complete blood count were determined. Percutaneous liver biopsy was done on all patients for histologic analysis and measurement of hepatic iron concentration and hepatic iron index. HFE genotyping for the C282Y and H63D mutations was done on all patients by using genomic DNA samples.
  
  
  RESULTS
  Of the 66 patients with hemochromatosis diagnosed on the basis of serum iron studies and liver biopsy findings, 60 (91%) were C282Y homozygotes, 2 (3%) were compound heterozygotes, 1 (1.5%) was a C282Y heterozygote, 2 (3%) were H63D heterozygotes, and 1 (1.5%) was negative for both mutations. Of the 132 patients with liver disease, 6 (5%) were C282Y homozygotes, 8 (6%) were compound heterozygotes, 6 (5%) were C282Y heterozygotes, 5 (4%) were H63D homozygotes, 20 (15%) were H63D heterozygotes, and 87 (66%) were negative for both mutations. All 66 C282Y homozygotes had an elevated hepatic iron concentration, and 65 of the 66 patients (98%) had a transferrin saturation of at least 45%. Ten of the 66 patients (15% [95% CI, 7.5% to 26%]) had a hepatic iron index less than 1.9 mmol/kg per year; hemochromatosis was not suspected in 6 of the 10 patients before genotyping. Cirrhosis or substantial hepatic fibrosis was not seen in any (0% [CI, 0% to 18%]) of the 19 patients younger than 40 years of age who were homozygous for the C282Y mutation.
  
  
  CONCLUSIONS
  All 66 patients homozygous for the C282Y mutation of HFE had an elevated hepatic iron concentration, but approximately 15% of these patients did not meet a previous diagnostic criterion for hemochromatosis (hepatic iron index > 1.9 mmol/kg per year). Determination of HFE genotype is clinically useful in patients with liver disease and suspected iron overload and may lead to identification of otherwise unsuspected C282Y homozygotes.
authors.affiliation: Saint Louis University School of Medicine, Missouri, USA. baconbr@slu.edu
authors.forename: B R
authors.initials: BR
authors.lastname: Bacon
authors.forename: J K
authors.initials: JK
authors.lastname: Olynyk
authors.forename: E M
authors.initials: EM
authors.lastname: Brunt
authors.forename: R S
authors.initials: RS
authors.lastname: Britton
authors.forename: R K
authors.initials: RK
authors.lastname: Wolff
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D006432:Hemochromatosis / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007501:Iron / Q000378:metabolism; D008107:Liver Diseases / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D013223:Statistics as Topic
chemical_list: D007501:Iron