In terms of the specific magnitude, a recent large-scale meta-analysis found that ALDH2-2 genotype reduced the risk of alcoholism by 25%-90%. Indeed, in over 4,000 individuals, only 3 cases of alcoholism were identified for ALDH2-2 homozygotes (Luczak et al., 2006). Of note, as with ADH genes, this protective effect generally pertains to individuals of East Asian ancestry for whom the ALDH2-2 allele is relatively common. Conversely, this polymorphism is rare in individuals of European or African ancestry (Oota et al., 2004). Interestingly, despite its strong putative protective effect, there is evidence the effects of ALDH2 status interact with environmental influences also. Higuchi et al. (1994) report that, from 1979 to 1992, the percentage of Japanese individuals with alcohol dependence who possessed an ALDH2-2 allele increased from 2.5% to 13%, suggesting that the protective effect of the polymorphism was reduced by the greater social acceptability of alcohol use in Japanese culture.
