Impacts of interactions between ADH1B and ALDH2 genotypes on alcohol flushing, alcohol reeking on the day after drinking, and age distribution in Japanese alcohol-dependent men.

OBJECTIVE

This study sought to evaluate the impacts of interactions between the alcohol dehydrogenase-1B (rs1229984) genotype and the aldehyde dehydrogenase-2 (rs671) genotype on alcohol flushing, alcohol reeking on the day after drinking, and the age distribution in alcohol-dependent patients.

METHODS

The study subjects were 4107 Japanese alcohol-dependent men who underwent alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 genotyping: 4051 patients were asked about their current or former tendency to experience facial flushing after drinking a glass of beer, and 969 patients were asked about whether they had ever been told that they reeked of alcohol more than 12 hours after they had stopped drinking.

RESULTS

Current, former, and never flushing were reported in 3.5, 14.9, and 81.5%, respectively, of the subject, and alcohol reeking after more than 12 hours in 36.1% of the subjects. The fast-metabolizing ADH1B*2(+) genotype (*1/2 or 2/2) and the inactive ALDH22(+) genotype (1/2 or 2/2) affected the multivariate odds ratios for current or former flushing [odds ratio, 95% confidence interval = 2.27 (1.79-2.86) and 23.0 (18.6-28.5), respectively, vs. 2(-) genotype] and for alcohol reeking [0.39 (0.29-0.52) and 1.56 (1.09-2.25), respectively, vs. 2(-) genotype]. An age-dependent decrease in the ADH1B2(-) and ALDH22(-) combination from 32.3% in the 30-39-year age group to 12.5% in the 70-79-year age group and an age-dependent increase in the ADH1B2(+) and ALDH22(-) combination from 52.5% in the 30-39-year age group to 70.5% in the 70-79-year age group were observed (P < 0.0001 for trend). The frequencies of the ADH1B2(-) and ALDH22(+) combination (4.7-6.2%) and the ADH1B2(+) and ALDH22(+) combination (8.9-12.0%) did not change markedly with increasing age.

CONCLUSION

Interactions between the alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 genotypes modified alcohol flushing, alcohol reeking on the day after drinking, and the age distribution. These findings support the protective roles of the ADH1B2(+) and ALDH22(+) genotypes against the development of alcohol dependence.