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 ADH₂¹ allele is common in Caucasians, while the atypical ADH₂² allele is predominant in Orientals. The ADH₂² produces the β₂ subunit, which is catalytically far more active than the β₁ subunit produced by the ADH₂¹ 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 ADH₂¹ 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.