Hereditary hemochromatosis: effect of excessive alcohol consumption on disease expression in patients homozygous for the C282Y mutation.
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.
Scotet
Virginie
V
INSERM EMI 01-15, Laboratoire de Génétique Moléculaire, CHU Morvan, Brest, France.
Mérour
Marie-Christine
MC
Mercier
Anne-Yvonne
AY
Chanu
Brigitte
B
Le Faou
Thérèse
T
Raguénes
Odile
O
Le Gac
Gérald
G
Mura
Catherine
C
Nousbaum
Jean-Baptiste
JB
Férec
Claude
C
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
D014168:Transferrin; D005293:Ferritins; D007501:Iron; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase