Direct determination of usual (Caucasian-type) and atypical (Oriental-type) alleles of the class I human alcohol dehydrogenase-2 locus.

Two types of alleles exist in the human alcohol dehydrogenase-2 (ADH2) locus. The usual ADH12 allele is common in Caucasians, while the atypical ADH22 allele is predominant in Orientals. The ADH22 produces the beta 2 subunit, which is catalytically far more active than the beta 1 subunit produced by the ADH12 gene. The racial difference in alcohol-related problems could be related to the genetic differences in ADH and other ethanol-metabolizing enzymes. In order to examine the possibility, a method for determining ADH2 genotypes was developed. Two 21-base synthetic oligonucleotides, one complementary to the usual ADH12 allele and the other complementary to the atypical ADH22 allele, were used as specific probes for in-gel hybridization analysis of human genomic DNA from peripheral blood. Under appropriate hybridization conditions, these two probes can hybridize to their specific complementary alleles and, thus, allow the genotyping of the ADH2 locus. Genotypes of the ADH2 locus of 49 unrelated Japanese individuals were determined. The frequency of the atypical ADH22 gene was found to be 0.71 in the Japanese population examined.