The ADH1B*2 and ADH1B*3 alleles have demonstrated a protective relation with alcohol dependence and related phenotypes in Asian and Caucasian samples and African-American samples respectively, and both alleles have been observed in the studied Native American populations. The ADH1B*2 allele was observed in both the California Indian and Southwest American Indian populations. The ADH1B*3 allele, which has only been observed in the California Indian population has been associated with reduced risk for alcohol dependence, reduced alcohol consumption, and reduced risk for alcohol withdrawal [43-44]. Studies of other Native American samples, however, have not observed the presence of the ADH1B*3 allele in their samples [45]. Additionally, a polymorphism in the promoter region of ADH4 (rs3762894) that has been shown to produce a more active version of the ADH enzyme [46] has shown a protective association with alcohol misuse phenotypes in multiple Caucasian and Native American populations. This polymorphism has shown evidence of association with reduced risk for alcohol withdrawal in the California Indian population [43] and with reduced risk for alcohol dependence in the Southwest American Indian and Plains Indian populations [45]. Although an initial study suggested a relation between a functional polymorphism in ADH1C (rs698; [47]), subsequent studies have failed
