The contribution of polymorphism in the alcohol dehydrogenase β subunit to alcohol sensitivity in a Japanese population

In humans, ingested alcohol is mainly metabolized by the combination of class I alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). In Orientals, there are highly frequent polymorphisms both in the class I ADH β subunit (ADH₂) and in the low K_m ALDH (ALDH2). We characterized the three genotypes of ALDH2 in a Japanese population. In the present study, we evaluated the effects of the ADH₂ polymorphism in the same population (424 males and 100 females) controlling for the effects of the ALDH2 polymorphism. In the ALDH2¹/ALDH2² group, the frequency of facial flushing with one glass of beer was significantly higher in the ADH₂ ¹/ADH₂ ² and ADH₂ ²/ADH₂ ² genotype than in the ADH₂ ¹/ADH₂ ¹ genotype. Likewise, the proportion of persons with positive results for ethanol-induced cutaneous erythema differed significantly depending on the ADH₂ genotype in both the ALDH2¹/ALDH2¹ and ALDH2¹/ ALDH2² genotypes. However, drinking habits were not significantly associated with the ADH₂ genotype, suggesting that the ADH₂ genotype influences the metabolism of ethanol only in the peripheral tissues. Received: 25 April 1995 / Revised: 25 September 1995