Association between genetic variation in ALDH1A1 (on chromosome 9q21.13) and inter-individual differences in the vulnerability to alcohol dependence and other alcohol-related phenotypes has been investigated in several studies. While there are three alternative splice patterns producing two ALDH1A1 isoforms [7], ALDH1A1 is highly conserved in humans. Two promoter polymorphisms have recently been correlated with the development of alcohol dependence in south-west Californian Indians [8] and other populations [1,9]. Spence and colleagues [1] sequenced the ALDH1A1 promoter region in Asian, Caucasian and African-American alcoholics and control subjects. They discovered two rare promoter polymorphisms, ALDH1A1*2 and ALDH1A1*3 (only detected in African Americans). While no association was observed between ALDH1A1*2 and alcohol dependence, there was a nominally significant difference in ALDH1A1*3 allelic frequency between alcoholics (6 per cent) and controls (0), and the ALDH1A1*3 polymorphism resulted in reduced ALDH1A1 expression. Ehlers et al. replicated this study in a south-west Californian Indian population of alcoholics and controls and observed a protective role for the ALDH1A1*2 polymorphism, whereby individuals with an ALDH1A1*2 allele reported lower rates of alcohol dependence, drank fewer drinks per session and
