CHARACTERIZATION OF THE 3 GENOTYPES OF LOW K-M ALDEHYDE DEHYDROGENASEIN A JAPANESE POPULATION

A deficiency in low K-m aldehyde dehydrogenase (ALDH2) is regarded as the main factor responsible for ''Oriental flushing'' and other sympto ms due to alcohol sensitivity. In this study, the relationship of the ALDH2 genotype to alcohol-associated symptoms and drinking behavior wa s investigated in 524 Japanese workers, using a new, rapid, and noniso topic polymerase chain reaction (PCR) method. Differences in the frequ ency of alcohol associated manifestations between the normal homozygot e and the other deficient types were apparent. In addition, among the ALDH2-deficient individuals, the atypical homozygote was obviously mor e hypersensitive to alcohol than the heterozygote, judging from the fr equency of flushing or other drinking-associated manifestations with a small dose of alcohol. Drinking frequency also apparently decreased i n the following order: typical homozygote, heterozygote, atypical homo zygote. Similarly, mean amounts of alcohol consumption also decreased in the same order, although considerable variation existed within the typical homozygote and the heterozygote group. In contrast, neither th e manifestations nor the drinking behavior were, in general, influence d by polymorphism of the alcohol dehydrogenase beta-subunit (ADH(2)) g ene in males. These findings further indicate the important contributi on of the ALDH2 genotype to alcohol sensitivity in Orientals.