Blood Ethanol Levels of Nonabstinent Japanese Alcoholic Men in the Morning After Drinking and Their ADH1B and ALDH2 Genotypes

Aims: Genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B, rs1229984) and aldehyde dehydrogenase-2 (ALDH2, rs671) affect ethanol (EtOH) metabolism and susceptibility to alcoholism. Methods: We evaluated associations between ADH1B/ALDH2 genotypes and the blood EtOH levels of 805 Japanese alcoholic men in the morning after they had drunk within the previous 34 h. Results: Age-adjusted usual alcohol consumption did not differ according to ADH1B/ALDH2 genotypes. Higher blood EtOH levels persisted for longer periods in the ADH1B*1/*1 carriers (n = 246) than in the ADH1B*2 carriers (n = 559). Blood EtOH levels did not differ by ALDH2 genotype. The blood EtOH levels ≥0.3 mg/ml (criterion for drunk driving in Japanese law) were observed (40% vs. 14–17%, P < 0.0001) in a higher proportion of the ADH1B*1/*1 carriers than of the ADH1B*2 carriers after a 12.1-to-18-h interval since the last drink. Multivariate analyses showed that the EtOH levels heightened by 0.500 mg/ml in the presence of ADH1B*1*1 and by 0.248 mg/ml in the presence of cirrhosis, and lowered by 0.120 mg/ml per 10-year age increase, by 0.087 mg/ml per 10-kg body-weight increase and by 0.673 mg/ml per 10-h interval since the last drink. The odds ratio (95% confidence interval) for an EtOH level ≥0.3 mg/ml was 3.44 (2.34–5.04) in the presence of ADH1B*1/*1, 2.01 (1.28–3.14) in the presence of cirrhosis, 0.59 (0.49–0.71) per 10-year age increase, 0.80 (0.68–0.95) per 10-kg body-weight increase and 0.10 (0.07–0.15) per 10-h interval since the last drink. Conclusion: The longer-than-expected EtOH lingering in the blood of the ADH1B*1/*1 alcoholics may exacerbate alcohol-related problems, including drunk driving.