As with the ADH genes, there are many non-coding variations in the ALDH2 gene. Some of these noncoding variations may affect gene expression, thereby modulating acetaldehyde elimination. For example, one variant in the ALDH2 promoter region that occurs in all major ethnic groups affects gene expression and may influence the risk for alcoholism (Chou et al. 1999; Harada et al. 1999). Noncoding ALDH2 variations also could affect ethanol metabolism in people of European or African descent, who rarely carry the ALDH2*2 allele. In fact, a recent study of six SNPs in a European population confirmed the absence of ALDH2*2 but demonstrated that two individual SNPs and a haplotype consisting of the minor alleles at five DNA sites are associated with elevated BACs after oral ingestion of alcohol (Dickson et al. 2006). The SNPs had a small effect on self-reported intoxication but no significant effect on alcohol dependence. Similar studies in other populations clearly are needed to further explore these issues.
