title: Hereditary hemochromatosis: effect of excessive alcohol consumption on disease expression in patients homozygous for the C282Y mutation.
abstract: Hereditary hemochromatosis is a common inherited disorder characterized by iron overload. A single mutation (C282Y) in the HFE gene is present in 80-95% of cases in populations of northern European extraction. The disorder presents a large phenotypic heterogeneity, and its expression can be influenced by environmental factors. This 1977-2002 study aimed to identify the influence of alcohol consumption on expression of the disease. The authors retrospectively registered 378 C282Y-homozygous patients treated in a blood center of western Brittany, France. In this cohort, 33 patients reported excessive alcohol consumption (8.7%). Those subjects presented significantly increased iron parameters (serum ferritin: 1745.2 vs. 968.7 microg/liter, p< 0.0001; serum iron: 39.9 vs. 36.0 micromol/liter, p = 0.0040; transferrin saturation: 87.1 vs. 80.1%, p = 0.0071) and elevated liver enzymes (alanine aminotransferase: 66.3 vs. 41.1 IU/liter, p = 0.0003; aspartate aminotransferase: 56.2 vs. 34.9 IU/liter, p = 0.0002). Their risk of skin pigmentation was also higher (odds ratio = 3.4, p = 0.0006). Results remained unchanged after adjustment. This study provides precise quantitative data about the impact of alcohol on expression of hereditary hemochromatosis in C282Y-homozygous patients. Excessive alcohol consumption accentuates disease expression and therefore the risk of cirrhosis and cancer. Consequently, these patients should be encouraged to consume very moderate quantities of alcohol.
authors.affiliation: INSERM EMI 01-15, Laboratoire de Génétique Moléculaire, CHU Morvan, Brest, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Scotet
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Mérour
authors.forename: Anne-Yvonne
authors.initials: AY
authors.lastname: Mercier
authors.forename: Brigitte
authors.initials: B
authors.lastname: Chanu
authors.forename: Thérèse
authors.initials: T
authors.lastname: Le Faou
authors.forename: Odile
authors.initials: O
authors.lastname: Raguénes
authors.forename: Gérald
authors.initials: G
authors.lastname: Le Gac
authors.forename: Catherine
authors.initials: C
authors.lastname: Mura
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Nousbaum
authors.forename: Claude
authors.initials: C
authors.lastname: Férec
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood; D000428:Alcohol Drinking / Q000009:adverse effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D016009:Chi-Square Distribution; D004198:Disease Susceptibility; D005260:Female; D005293:Ferritins / Q000097:blood; D005602:France / Q000453:epidemiology; D006432:Hemochromatosis / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007501:Iron / Q000097:blood; D019190:Iron Overload / Q000235:genetics; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D010859:Pigmentation Disorders / Q000453:epidemiology / Q000209:etiology; D012189:Retrospective Studies; D012307:Risk Factors; D018709:Statistics, Nonparametric; D014168:Transferrin / Q000378:metabolism
chemical_list: D014168:Transferrin; D005293:Ferritins; D007501:Iron; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase