ALCOHOL AND ALDEHYDE DEHYDROGENASE POLYMORPHISMS AND THE RISK FOR ALCOHOLISM

Objective: The authors studied a large number of Japanese alcoholic pa tients and comparison subjects to establish the genotype frequencies o f alcohol dehydrogenase-2 (ADH2) and mitochondrial aldehyde dehydrogen ase (ALDH2) and to quantify the relative risk for alcoholism from the results. Method: The subjects were 655 alcoholic patients and 461 comp arison subjects. ADH2 and ALDH2 were genotyped by the combination of p olymerase chain reaction and hybridization methods. Results: Active AL DH2 and usual ADH2 were significantly more frequent in the alcoholic p atients. Inactive ALDH2 was not always associated with a low risk of a lcoholism, and active ALDH2 was not always associated with high risk. In individuals with heterozygous inactive ALDH2 and usual ADH2, the od ds ratio for alcoholism was high. Conclusions: The risk for alcoholism in Japanese has been accurately estimated on the basis of the genotyp e frequencies of ADH2 and ALDH2. Many Japanese may be protected from a lcoholism by inactive ALDH2 and by higher frequencies of atypical ADH2 .