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.
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.
Authors: Nicholas J W Rattray; Georgia Charkoftaki; Zahra Rattray; James E Hansen; Vasilis Vasiliou; Caroline H Johnson Journal: Curr Pharmacol Rep Date: 2017-04-07
Authors: Michael V Holmes; Caroline E Dale; Luisa Zuccolo; Richard J Silverwood; Yiran Guo; Zheng Ye; David Prieto-Merino; Abbas Dehghan; Stella Trompet; Andrew Wong; Alana Cavadino; Dagmar Drogan; Sandosh Padmanabhan; Shanshan Li; Ajay Yesupriya; Maarten Leusink; Johan Sundstrom; Jaroslav A Hubacek; Hynek Pikhart; Daniel I Swerdlow; Andrie G Panayiotou; Svetlana A Borinskaya; Chris Finan; Sonia Shah; Karoline B Kuchenbaecker; Tina Shah; Jorgen Engmann; Lasse Folkersen; Per Eriksson; Fulvio Ricceri; Olle Melander; Carlotta Sacerdote; Dale M Gamble; Sruti Rayaprolu; Owen A Ross; Stela McLachlan; Olga Vikhireva; Ivonne Sluijs; Robert A Scott; Vera Adamkova; Leon Flicker; Frank M van Bockxmeer; Christine Power; Pedro Marques-Vidal; Tom Meade; Michael G Marmot; Jose M Ferro; Sofia Paulos-Pinheiro; Steve E Humphries; Philippa J Talmud; Irene Mateo Leach; Niek Verweij; Allan Linneberg; Tea Skaaby; Pieter A Doevendans; Maarten J Cramer; Pim van der Harst; Olaf H Klungel; Nicole F Dowling; Anna F Dominiczak; Meena Kumari; Andrew N Nicolaides; Cornelia Weikert; Heiner Boeing; Shah Ebrahim; Tom R Gaunt; Jackie F Price; Lars Lannfelt; Anne Peasey; Ruzena Kubinova; Andrzej Pajak; Sofia Malyutina; Mikhail I Voevoda; Abdonas Tamosiunas; Anke H Maitland-van der Zee; Paul E Norman; Graeme J Hankey; Manuela M Bergmann; Albert Hofman; Oscar H Franco; Jackie Cooper; Jutta Palmen; Wilko Spiering; Pim A de Jong; Diana Kuh; Rebecca Hardy; Andre G Uitterlinden; M Arfan Ikram; Ian Ford; Elina Hyppönen; Osvaldo P Almeida; Nicholas J Wareham; Kay-Tee Khaw; Anders Hamsten; Lise Lotte N Husemoen; Anne Tjønneland; Janne S Tolstrup; Eric Rimm; Joline W J Beulens; W M Monique Verschuren; N Charlotte Onland-Moret; Marten H Hofker; S Goya Wannamethee; Peter H Whincup; Richard Morris; Astrid M Vicente; Hugh Watkins; Martin Farrall; J Wouter Jukema; James Meschia; L Adrienne Cupples; Stephen J Sharp; Myriam Fornage; Charles Kooperberg; Andrea Z LaCroix; James Y Dai; Matthew B Lanktree; David S Siscovick; Eric Jorgenson; Bonnie Spring; Josef Coresh; Yun R Li; Sarah G Buxbaum; Pamela J Schreiner; R Curtis Ellison; Michael Y Tsai; Sanjay R Patel; Susan Redline; Andrew D Johnson; Ron C Hoogeveen; Hakon Hakonarson; Jerome I Rotter; Eric Boerwinkle; Paul I W de Bakker; Mika Kivimaki; Folkert W Asselbergs; Naveed Sattar; Debbie A Lawlor; John Whittaker; George Davey Smith; Kenneth Mukamal; Bruce M Psaty; James G Wilson; Leslie A Lange; Ajna Hamidovic; Aroon D Hingorani; Børge G Nordestgaard; Martin Bobak; David A Leon; Claudia Langenberg; Tom M Palmer; Alex P Reiner; Brendan J Keating; Frank Dudbridge; Juan P Casas Journal: BMJ Date: 2014-07-10