Another well-known polymorphism is in the ALDH2 gene encoding aldehyde dehydrogenase 2 family (mitochondrial). The ALDH2*2 allele, which substitutes lysine for glutamate at position 504 (Lys504), results in a nearly inactive protein subunit that is unable to metabolize acetaldehyde (149). This allele is relatively common in Asians but nearly absent in people of European or African descent (69, 102) and is strongly associated with a reduced risk for alcohol dependence (33). Polymorphisms in other ADH genes have also been associated with alcohol dependence (36, 77). Studies have shown that variation in the ADH genes contributes substantially to variation in alcohol metabolism and consequently affects the risk for alcohol dependence. Although the variants ADH1B Arg48His and ADH1C Arg272Gln/Ile350Val are known to have a major effect on enzyme activity in vitro, these variants account for only a very small amount of the genetic variance in in vivo metabolism (18, 94). In vivo studies in Europeans demonstrated that variants in ADH7 are associated with the early stages of alcohol metabolism, with additional effects in ADH1A, ADH1B, and ADH4 (18). Postabsorptive alcohol metabolism is
