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Polymorphism at the ADH2 and ADH3 loci of alcohol dehydrogenase (ADH) has been shown to have an effect on the predisposition to alcoholism in Asian individuals. However, the results are not conclusive for white individuals. We have analyzed the ADH genotype of 876 white individuals from Spain (n = 251), France (n = 160), Germany (n = 184), Sweden (n = 88), and Poland (n = 193). Peripheral blood samples from healthy controls and groups of patients with viral cirrhosis and alcohol-induced cirrhosis, as well as alcoholics with no liver disease, were collected on filter paper. Genotyping of the ADH2 and ADH3 loci was performed using polymerase chain reaction-restriction fragment length polymorphism methods on white cell DNA. In healthy controls, ADH2*2 frequencies ranged from 0% (France) to 5.4% (Spain), whereas ADH3*1 frequencies ranged from 47. 6% (Germany) to 62.5% (Sweden). Statistically significant differences were not found, however, between controls from different countries, nor between patients with alcoholism and/or liver disease. When all individuals were grouped in nonalcoholics (n = 451) and alcoholics (n = 425), ADH2*2 frequency was higher in nonalcoholics (3.8%) than in alcoholics (1.3%) (P =.0016), whereas the ADH3 alleles did not show differences. Linkage disequilibrium was found between ADH2 and ADH3, resulting in an association of the alleles ADH2*2 and ADH3*1, both coding for the most active enzymatic forms. In conclusion, the ADH2*2 allele decreases the risk for alcoholism, whereas the ADH2*2 and ADH3*1 alleles are found to be associated in the European population.

Steatosis is the most common although inconstant hepatic lesion induced by chronic alcohol consumption. Alcoholic cirrhosis is found in only 20 to 30% of chronic alcohol misusers, which points to the influence of both environmental and genetic factors. Apolipoprotein E (apo E) presents an important polymorphism with three common alleles, epsilon 4, epsilon 3 and epsilon 2. Its modulation role on triglyceride-rich lipoproteins and cholesterol-containing lipoproteins is linked with its interaction with cellular specific receptors. This work aims at studying a possible correlation between apo E polymorphism and alcoholic cirrhosis. The three common alleles were identified by enzymatic amplification (PCR) of genomic DNA from blood samples and analysis of restriction profiles. The distribution of alleles and genotypes was performed in 35 Caucasian cirrhotic patients (medium age 57 years) and compared with the usual distribution of apo E phenotypes in European Caucasian populations. The results show lower epsilon 4 and epsilon 2 allele frequencies and higher epsilon 3 allele frequency in Caucasian alcoholic cirrhotics.