The second SNP of interest due to its association with both phenotypes tested, rs8187974, is located in an intron at a splice site in ALDH1A1. ALDH1A1 is the primary cytosolic aldehyde dehydrogenase, as compared to the mitochondrial form ALDH2. Although common polymorphisms in ALDH1A1 with large effects on alcohol behavior have been described in several non-European populations, these polymorphisms are not present in Caucasians. There are alcohol flushing Caucasians, however, who have much lower ALDH1 enzymatic activity (Yoshida et al., 1989). It is unlikely that rs8187974 is responsible for this observation, however, since minor allele carriers show increased max drinks and more severe alcohol dependence. If this SNP has a real biological effect it is likely to increase the rate of ALDH1 activity or expression. The SNP’s location raises the possibility that it results in an alternately spliced form of the enzyme in the 1% of the population carrying the minor allele, or that it results in a more efficiently translated mRNA.
