Two polymorphisms in genes encoding alcohol metabolizing enzymes, alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase 2 (ALDH2) have been associated with differences in alcohol consumption and dependence [35-37]. The ADH1B Arg48His (rs1229984), results in increased oxidation of alcohol to acetaldehyde, while the other variant, ALDH2 Glu504Lys (rs671), is associated with decreased enzymatic conversion of acetaldehyde to acetate. Consequently both variants, most prevalent among East Asians [38], cause the accumulation of acetaldehyde, which induces aversive reactions to alcohol consumption including flushing, nausea, and palpitations. This aversive response typically decreases alcohol consumption and protects against the development of addiction. Although relatively uncommon in non-Asians, the protective effects of the ADH1B allele on alcohol dependence and consumption were recently supported within a meta-analysis of individuals of European and African American descent [39] and more recently, at genomewide significant levels in a German population [40] and in an independent genomewide association study of European and African-American subjects [41••]. In addition to ADH1B and ALDH2, other variants in alcohol dehydrogenase encoding genes, such as ADH1A, ADH1C, ADH4, ADH5, and ADH7 have also been sporadically associated with alcohol dependence [36, 37, 42-44].
