In addition to the widely replicated associations between the rs1229984 and rs671 with alcoholism risk, certain variants in other genes encoding alcohol-metabolizing enzymes, such as ADH1C, ADH4, and ADH5, also have been linked to alcohol dependence in other populations. Alterations in the ADH1C gene, which encodes the γ subunit of alcohol dehydrogenase, can change alcohol metabolism by the encoded protein and have been associated with alcoholism, although these effects are not as pronounced as those noted with ADH1B*2 (Edenberg 2007). For instance, the ADH1C variants rs698 and rs1693482 also alter the amino acid sequence of the encoded protein and occur with high frequency in European American populations (minor allele ≈ 47 percent). Likewise, variants in ADH4 and ADH5 sporadically have been linked to alcoholism. For example, Macgregor and colleagues (2009) reported associations between SNPs in these genes and alcohol dependence symptoms as well as quantity, frequency, and maximum drinks, whereas two other independent studies reported highly significant associations between ADH4 variants and alcohol dependence (Edenberg et al. 2006; Luo et al. 2006). The study by Mcgregor and colleagues (2009) also is among the few studies of non-Asian populations that demonstrate an association between ADH and ALDH2 polymorphisms and problem drinking.
