Genetic polymorphism of alcohol dehydrogenase in Europeans: The ADH2*2 allele decreases the risk for alcoholism and is associated with ADH3*1

Polymorphism at the ADH2 and ADH3 loci of alcohol dehydrogenase (ADH) has b een shown to have an effect on the predisposition to alcoholism in Asian in dividuals. However, the results are not conclusive for white individuals. W e have analyzed the ADH genotype of 876 white individuals from Spain (n = 2 51), 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 AD H2 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 diff erent countries, nor between patients with alcoholism and/or liver disease. When all individuals were grouped in nonalcoholics (n = 451) and alcoholic s (n = 425), ADH2*2 frequency was higher in nonalcoholics (3.8%) than in al coholics (1.3%) (P =.0016), whereas the ADH3 alleles did nor show differenc es. 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 act ive enzymatic forms. In conclusion, the ADH2*2 allele decreases the risk fo r alcoholism, whereas the ADH2*2 and ADH3*1 alleles are found to be associa ted in the European population.