Alcohol abuse is a common disorder influenced by both genetics and environment. Despite strong evidence of a role for genetics in abuse liability, few specific susceptibility candidate genes for alcoholism have emerged. Natural variations in components of the ethanol metabolism machinery are among the very few identified genetic causes of the variation in alcohol abuse liability in humans (recently reviewed by Pautassi et al., 2010). Ethanol is metabolized to acetaldehyde by alcohol dehydrogenase (ADH); subsequently, acetaldehyde is metabolized to acetate by an aldehyde dehydrogenase (ALDH). Certain isoforms of ADH that are more enzymatically active are protective for susceptibility for alcoholism. Similarly, ALDH isoforms with decreased enzymatic activity also decrease disease liability. Both types of alleles are predicted to increase acetaldehyde levels, which appear to be aversive, suggesting a mechanism for the decrease in susceptibility to alcohol abuse disorders in individuals carrying them. While there are significant correlations between inheritance of these ADH or ALDH alleles and rates of alcohol abuse (Chen et al., 2009; Crabb et al., 2004; Edenberg et al., 2006; Kuo et al., 2008), there is little experimental detail on the behavioral consequences during acute ethanol treatment of variation in alcohol metabolism.
