Alcoholism is a major public health problem globally. Many genes have allele frequency variation that has been associated with risk of developing either alcoholism or complications of alcoholism. The ethanol metabolizing genes, especially the alcohol dehydrogenase (ADH) genes and the aldehyde dehydrogenase 2 (ALDH2) gene, are the strongest such associations (Couzigou et al., 1994; Long et al., 1998; Reich et al., 1998; Chen et al., 1999; Luo et al., 2006). The major metabolic pathway for ethanol is degradation by ADH enzymes to acetaldehyde followed by degradation of that intermediate metabolite to acetate by ALDH enzymes. The mitochondrial ALDH2, encoded by the ALDH2 gene on chromosome 12, has the lowest Km (~1μmol/L) for acetaldehyde (Algar & Holmes, 1989). The variants at ADH genes and at ALDH2 that are associated with alcoholism appear to interact by increasing the transient levels of the toxic acetaldehyde.
