Probably the best known variation of alcohol-metabolizing enzymes is associated with the ALDH2 gene. A coding variant known as the ALDH2*2 allele leads to the substitution of lysine for glutamate at position 504.6 This substitution results in the production of a nearly inactive ALDH2 enzyme that no longer oxidizes acetaldehyde to acetate. Studies on liver extracts demonstrated that the ALDH2*2 variant was nearly dominant—that is, people who carry one ALDH2*1 and one ALDH2*2 allele (i.e., who are heterozygous) have almost no detectable ALDH2 activity in the liver; people who carry two copies of the ALDH2*2 allele (i.e., who are homozygous) have no detectable activity (Crabb et al. 1989). Studies in which the alleles were introduced into cultured cells confirmed this observation (Xiao et al. 1995, 1996). The inactive ALDH2*2 allele is relatively common in people of Chinese, Japanese, and Korean descent but is essentially absent in people of European or African descent (Oota et al. 2004; Hurley et al. 2002). People carrying an ALDH2*2 allele show an alcohol flush reaction, even when they consume only relatively small amounts of alcohol
