The ALDH2 variant leading to decreased risk of alcohol dependence, ALDH2*2, has been further characterized since its initial discovery in the 1980s. ALDH2*2 is a coding variant resulting from the substitution of lysine for glutamate at position 504, resulting in a nearly inactive ALDH2 enzyme and leading to markedly elevated acetaldehyde levels in the blood with the consumption of small amounts of alcohol. The allele is common in people of East Asian descent, but it is essentially nonexistent in people of European or African descent.14 The protective effect of this allele is strong and has been replicated in multiple studies.15–17 The odds ratio of alcohol dependence for subjects with 1 ALDH2*2 allele is 0.33, and there are almost no documented cases of people with alcohol dependence who are homozygous for ALDH2*2.15–17 This allele interacts with a nonsynonymous gene variant for the ADH1 enzyme, ADH1B*1, by further decreasing the odds ratio of alcohol dependence to 0.05 in the presence of both alleles.15 The protective effect of the ALDH2*2 allele is susceptible to environmental pressures. A study by Higuchi and colleagues18 found
