OBJECTIVE: The authors studied a large number of Japanese alcoholic
patients and comparison subjects to establish the genotype frequencies of
alcohol dehydrogenase-2 (ADH2) and mitochondrial aldehyde dehydrogenase
(ALDH2) and to quantify the relative risk for alcoholism from the results.
METHOD: The subjects were 655 alcoholic patients and 461 comparison
subjects. ADH2 and ALDH2 were genotyped by the combination of polymerase
chain reaction and hybridization methods. RESULTS: Active ALDH2 and usual
ADH2 were significantly more frequent in the alcoholic patients. Inactive
ALDH2 was not always associated with a low risk of alcoholism, and active
ALDH2 was not always associated with high risk. In individuals with
heterozygous inactive ALDH2 and usual ADH2, the odds ratio for alcoholism
was high. CONCLUSIONS: The risk for alcoholism in Japanese has been
accurately estimated on the basis of the genotype frequencies of ADH2 and
ALDH2. Many Japanese may be protected from alcoholism by inactive ALDH2 and
by higher frequencies of atypical ADH2.