Polymorphisms of alcohol-metabolizing enzymes and the risk for alcoholism and alcoholic liver disease in Caucasian Spanish women.

Abstract

The relationship of polymorphisms of the genes that encode for alcohol-metabolizing enzymes and individual vulnerability to alcoholism and alcoholic liver disease (ALD) in women is unclear. We determined the genotypes of ADH1B, ADH1C, CYP2E1 (Dra-I and Pst-I) and ALDH2 in a group of Caucasian Spanish women. We performed a cross-sectional case-control study. The study group was made of 220 women. Of these, 85 were alcoholic (27 without liver disease and 58 with alcoholic liver disease) and 135 were non-alcoholic (42 healthy controls and 93 with liver disease unrelated to alcohol). Genotyping of alcohol-metabolizing enzymes was performed using PCR-RFLP methods. The distribution of the allelic variants (alleles 1 and 2) in the whole subjects analyzed was: ADH1B 91.6% and 8.4%; ADH1C 58.4% and 41.6%; CYP2E1 Dra-I 15% and 85%; CYP2E1 Pst-I 96.8% and 3.2%; and ALDH2 100% and 0%, respectively. Carriage of genotypes containing the ADH1B*2 mutant allele significantly protected against alcoholism [odds-ratio (OR)=0.00; 95% confidence interval (95% CI): 0.00-0.94; p=0.02] but was associated with an increased risk for alcoholic liver disease among alcohol-dependent women [OR=0.43; 95% CI: 0.18-0.41; p=0.004]. Analysis of the remaining loci showed no significant associations. In Caucasian Spanish women the ADH1B*2 allele modulates the risk for alcohol dependence and for alcoholic liver disease. Given the small number of alcoholic women analyzed here, these data need further validation in larger cohorts.