title: Heterozygotes for HFE mutations have no increased risk of advanced alcoholic liver disease.
abstract: BACKGROUND
  Iron overload is common in the livers of alcoholics and may play a role in disease pathogenesis. An MHC like gene, HFE, has recently been identified that is mutated in most patients with hereditary haemochromatosis (C282Y in 90% and H63D in 45% of the remainder).
  
  
  OBJECTIVE
  To examine the hypothesis that these mutations determine hepatic iron status in alcoholics and play a role in pre-disposition to advanced alcoholic liver disease.
  
  
  METHODS
  The HFE gene was genotyped in 257 patients with alcoholic liver disease and 117 locally matched healthy volunteers. In addition, iron staining was scored (0-4) on biopsy specimens from fibrotic/cirrhotic patients with and without HFE mutations matched for age and sex.
  
  
  RESULTS
  Some 15.7% of fibrotic/cirrhotic patients were C282Y heterozygotes compared with 13.7% of controls (p = 0.77). One control and three patients were C282Y homozygotes. Of chromosomes without the C282Y mutation, 68/442 (15.4%) of patients' chromosomes carried the H63D mutation compared with 36/216 (16.6%) of control chromosomes (p = 0.91). Significant (> grade 1) hepatocyte iron staining was seen in 6/23 C282Y heterozygotes and 4/26 H63D heterozygotes compared with 4/23 controls.
  
  
  CONCLUSIONS
  Possession of a single copy of either of the two HFE mutations influences neither liver iron content nor the risk of fibrotic disease in alcoholics.
authors: Centre for Liver Research, University of Newcastle upon Tyne, UK.
authors: J
authors: J
authors: Grove
authors: A K
authors: AK
authors: Daly
authors: A D
authors: AD
authors: Burt
authors: M
authors: M
authors: Guzail
authors: O F
authors: OF
authors: James
authors: M F
authors: MF
authors: Bassendine
authors: C P
authors: CP
authors: Day
mesh_terms: D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D000071020:Hemochromatosis Protein; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000378:metabolism; D019190:Iron Overload / Q000235:genetics / Q000378:metabolism; D008108:Liver Diseases, Alcoholic / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D009154:Mutation / Q000235:genetics*; D012307:Risk Factors
chemical_list: C103673:HFE protein, human; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D007501:Iron