The variants in the alcohol metabolizing genes (ADH and ALDH) have clear functional consequences at the molecular and behavioral levels. This is the exception rather than the rule in terms of relating genetic variation to straightforward functional consequences of polymorphisms that have been identified for alcohol dependence. For example, a missense variant in (alcohol dehydrogenase 1B [ADH1B]) leads to the replacement of Arg48 with His48 in the encoded protein and reduces the risk for alcoholism in Asians, Native, European and African Americans. The hypothesized mechanism of action involves an increased aversive reaction when alcohol is consumed by the accumulation of the toxic alcohol metabolic by-product, acetaldehyde in the periphery which is due to a reduction in the function of polymorphic ADH enzyme. This mechanism of action is also the basis for the use of disulfiram, the first FDA-approved medication for alcohol dependence.
