Ethanol and acetaldehyde metabolism in chinese with different aldehyde dehydrogenase-2 genotypes

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the major enzymes responsible for ethanol metabolism in humans. Both enzymes exhibit genetic polymorphisms among racial populations. About half of the Chinese population lack mitochondrial ALDH2 activity and such a deficiency has been believed to be a negative risk factor for the development of alcoholism. To assess ethanol and acetaldehyde metabolism in Chinese with different ALDH2 genotypes, we genotyped 273 male adults at the ADH2, ADH3, and ALDH2 loci by using polymerase chain reaction-directed mutagenesis and restriction fragment length polymorphisms. Of the 143 individuals homozygous for both the ADH2*2 and the ADH3*1 alleles, 80, 55, and 8 were identified as ALDH2*1/*1, ALDH2*1/*2, and ALDH2*/*2, respectively. Five each from the above three ALDH2 genotypic subjects underwent alcohol elimination testing. Blood ethanol and acetaldehyde levels were determined at various times up to 130 min after intaking a low dose of ethanol (0.2 g/kg body weight) by using head-space gas chromatography and high-performance liquid chromatography with fluorescence detection, respectively. The mutant homozygotes of ALDH2*2/*2 and the heterozygotes exhibited significantly higher peak acetaldehyde concentrations and also greater areas under the blood concentrations-time curve (AUC) than did the normal homozygotes of ALDH2*1/*1, with the mutant homozygotes both being the largest. The mutant homozygotes displayed significantly higher peak ethanol levels and AUC compared to the normal homozygotes. Of the 17 subjective feeling items tested, palpitation, facial warming, effects of alcohol, and dizziness were found to be most pronounced among the mutant homozygotes.(ABSTRACT TRUNCATED AT 250 WORDS)