Substance abuse, which constitutes a major public health problem, is genetically influenced, but characterized by incomplete penetrance, phenocopies, heterogeneity, and polygenic inheritance. The alcohol dehydrogenase 1B and 1C genes (ADH1B and ADH1C) encode class I alcohol dehydrogenase beta and gamma subunits, respectively. These isoenzymes metabolize alcohol into acetaldehyde (among other physiological actions); acetaldehyde is then metabolized into acetate through the aldehyde dehydrogenase 2 gene (ALDH2). The gamma subunit encoded by ADH1C plays a key role in the oxidation catabolism of a wide variety of substrates, including ethanol, retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products. ADH1B appears to play the greatest role in modulating alcohol dependence risk among the ADH loci (review, Li et al., 2011). The ADH1C gene (formerly called ADH3), located on chromosome 4q21-q23, is adjacent to ADH1B and in the region of a gene cluster of the alcohol dehydrogenase subunits 6, 1A, 1B, 1C, and 7. The common form of a single nucleotide polymorphism (SNP: rs698, Ile350Val in exon 8, formerly known as ADH1C *1/*2) at the ADH1C gene locus is 350Val (G or *2). The
