title: Iron homeostasis and H63D mutations in alcoholics with and without liver disease.
abstract: OBJECTIVE
  To evaluate the prevalence of HFE gene mutation and indices of disturbed iron homeostasis in alcoholics with and without liver disease.
  
  
  METHODS
  One hundred and fifty-three heavy drinkers (defined as alcohol consumption > 80 g/d for at least 5 years) were included in the study. These comprised 78 patients with liver disease [liver disease alcoholics (LDA)] in whom the presence of liver disease was confirmed by liver biopsy or clinical evidence of hepatic decompensation, and 75 subjects with no evidence of liver disease, determined by normal liver tests on two occasions [non-liver disease alcoholics (NLDA)], were consecutively enrolled. Serum markers of iron status and HFE C282Y and H63D mutations were determined. HFE genotyping was compared with data obtained in healthy blood donors from the same geographical area.
  
  
  RESULTS
  Gender ratio was similar in both study groups. LDA patients were older than NLDA patients (52 +/- 10 years vs 48 +/- 11 years, P = 0.03). One third and one fifth of the study population had serum transferrin saturation (TS) greater than 45% and 60% respectively. Serum iron levels were similar in both groups. However, LDA patients had higher TS (51 +/- 27 vs 36 +/- 13, P < 0.001) and ferritin levels (559 +/- 607 ng/mL vs 159 +/- 122 ng/mL, P < 0.001), and lower total iron binding capacity (TIBC) (241 +/- 88 microg/dL vs 279 +/- 40 microg/dL, P = 0.001). The odds ratio for having liver disease with TS greater than 45% was 2.20 (95% confidence interval (CI): 1.37-3.54). There was no difference in C282Y allelic frequency between the two groups. However, H63D was more frequent in LDA patients (0.25 vs 0.16, P = 0.03). LDA patients had a greater probability of carrying at least one HFE mutation than NLDA patients (49.5% vs 31.6%, P = 0.02). The odds ratio for LDA in patients with H63D mutation was 1.57 (95% CI: 1.02-2.40).
  
  
  CONCLUSIONS
  The present study confirms the presence of iron overload in alcoholics, which was more severe in the subset of subjects with liver disease, in parallel with an increased frequency of H63D HFE mutation.
authors.affiliation: Unidade de Nutrição e Metabolismo, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Portugal.
authors.forename: Mariana Verdelho
authors.initials: MV
authors.lastname: Machado
authors.forename: Paula
authors.initials: P
authors.lastname: Ravasco
authors.forename: Alexandra
authors.initials: A
authors.lastname: Martins
authors.forename: Maria Rosário
authors.initials: MR
authors.lastname: Almeida
authors.forename: Maria Ermelinda
authors.initials: ME
authors.lastname: Camilo
authors.forename: Helena
authors.initials: H
authors.lastname: Cortez-Pinto
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000150:complications / Q000235:genetics* / Q000378:metabolism*; D019943:Amino Acid Substitution; D005260:Female; D005787:Gene Frequency; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000150:complications / Q000235:genetics / Q000378:metabolism; D008108:Liver Diseases, Alcoholic / Q000150:complications / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D007501:Iron