Genetic influences are first evident at the first step in the metabolism of alcohol. As noted above, alcohol is initially broken down in acetaldehyde by ADH. Of the multiple forms of the ADH, the class I isozymes (ADH1A, ADH1B, and ADH1C) play the predominant role in metabolizing alcohol (Edenberg, 2007; Lee et al., 2006). The genes responsible for these enzymes are closely linked on chromosome 4 and the ADH1B and ADH1C genes (coding for the respective isoenzymes) have been determined to have functional polymorphisms. In the case of ADH1B, three polymorphisms of the gene have been identified, of which two (ADH1B-2, ALDH1B-3) are associated with faster enzymatic activity compared to the ADH1B-1 allele, with both resulting in a 70- to 80-fold greater turnover rate. In the case of ADH1C, two variants have been characterized, ADH1C-1 and ADH1C-2, and there is evidence that ADH1C-1 is associated with approximately half the alcohol turnover compared to ADH1C-2. In addition, some Native American groups have been found to carry a third variant of the ADH1C gene (Osier et al., 2002), but that has not
