Impact of the alcohol-dehydrogenase (ADH) 1C and ADH1B polymorphisms on drinking behavior in nonalcoholic Japanese

A linkage disequilibrium (LD) between the alcohol-dehydrogenase 1B (ADH1B) and alcohol-dehydrogenase 1C (ADH1C) polymorphisms adds complexity to differentiating the significance of these two genetic polymorphisms on drinking behavior and alcoholism. We have recently shown the importance of the ADH1B polymorphism on habitual drinking in the Japanese population; however, the issue regarding the LD between the ADH1B and ADH1C polymorphisms remains to be clarified. Here, we conducted a cross-sectional study in 2,299 nonalcoholic Japanese individuals. Drinking behavior was examined with regard to haplotypes of the ADH1B and ADH1C polymorphisms. Strength of association was assessed by sex and alaehyde-dehydrogenase 2 (ALDH2) adjusted odds ratios (OR) and their 95% confidence intervals (CIs) for the haplotype of the ADH1B and ADH1C polymorphisms. The ORs for habitual drinking were significant for ADH1B*2(rapid), ADHIC*2(slow) (OR = 1.03; 95% CI: 1.01-1.05), ADHIB*1 (slow)-ADH1C*1 (rapid) (OR = 1.15; 95% CI: 1.14-1.16), and ADH1B*1 (slow)-ADH1C*2 (slow) (OR= 1.31; 95% CI: 1.29-1.32) compared with ADH1B*2 (rapid) ADH1C*1 (rapid). This trend was evident among mates. Similarly, a significantly increased risk of heavy drinking was observed for each haplotype compared with ADH1B*2 (rapid)-ADH1C*1 (rapid). In conclusion, this study showed a significant impact of the ADH1C polymorphism on habitual drinking, regardless of the ADH1B/ALDH2 polymorphisms.