The rs348449 polymorphism was nominally associated (p = 0.043 for the dominant model of inheritance; p = 0.13 for general association) where the AUDIT score genotypic means were 18.9, 24.4 and 22.0 for zero, one and two G alleles, respectively (Table 2). Significant differences in both the rs348449 genotypic and allelic frequencies were detected between the controls and the problem drinkers (Table 3). The frequency of the minor allele G was 1 per cent in controls compared with 7 per cent in the problem drinkers and 3.4 per cent in treated alcoholics. No G/G homozygotes were observed in the control and treated alcoholics groups. Problem drinkers were 7.8 times more likely to have the rs348449 G allele (OR = 7.87, 95 per cent CI 1.67-37.01, p = 0.003) and 7.4 times more likely to have the GG or GA genotype (p = 0.017). By contrast, the allelic and genotypic distributions in the treated alcoholics and control groups were not significantly different. Therefore, rs348449 may play a role in the consumption of high levels of alcohol (which can lead to dependence symptoms and alcohol-related problems) rather than the development of alcohol dependence.
