In Orientals, ALDH2 deficiency due to a common polymorphism frequently causes a flushing reaction after alcohol consumption and this aversive reaction is responsible for lower rates of alcoholism in individuals with the inactive ALDH2-2 allele. ALDH2 deficiency was detected in South American Indian populations; however, these findings have never been confirmed and a previous search for the Oriental ALDH2-2 allele in South American Indians was negative. Another goal of this project is to identify additional markers at ALDH2. This will enable us to identify haplotypes characteristic for the ALDH2-2 and ALDH2-1 alleles in different populations. Such an analysis can help reveal the origins and functional role of the variant ALDH2-2 allele. In this project, we have: (1) confirmed absence of ALDH2 activity in 3,139 Chachi South American Indians; (2) shown that the Oriental ALDH2-2 allele is either not present or present in low abundance across five populations of South American Indians; and (3) described a new amino acid substitution occurring on the ALDH2-2 genetic background and this allele is known as ALDH2-2 Taiwan.