{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:39:30Z","timestamp":1787009970604,"version":"build-2736575974"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,7]]},"abstract":"\n Objectives<\/jats:title>\n \n Given the high prevalence of fast-metabolizing\n alcohol dehydrogenase-1B*2 (ADH1B*2<\/jats:italic>\n ) and inactive\n aldehyde dehydrogenase-2*2 (ALDH2*2<\/jats:italic>\n ) alleles in East Asians, we evaluated how the\n ADH1B<\/jats:italic>\n \/\n ALDH2<\/jats:italic>\n genotypes and alcohol flushing might affect the development of alcohol dependence (AD).\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We evaluated how the\n ADH1B<\/jats:italic>\n \/\n ALDH2<\/jats:italic>\n genotypes and self-reported alcohol flushing affected history of drinking events and withdrawal symptoms and ICD-10 criteria in 4116 Japanese AD men.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The\n ADH1B*1\/*1<\/jats:italic>\n group and\n ALDH2*1\/*1<\/jats:italic>\n group were 1\u20135 years younger than the\n ADH1B*2<\/jats:italic>\n (+) and\n ALDH2*1\/*2<\/jats:italic>\n groups, respectively, for all of the ages at onset of habitual drinking, blackouts, daytime drinking, uncontrolled drinking, withdrawal symptoms, and first treatment for AD, and the current age. Blackouts were more common in the\n ADH1B*1\/*1<\/jats:italic>\n group and\n ALDH2*1\/*1<\/jats:italic>\n group. Daytime drinking, uncontrolled drinking, and withdrawal symptoms, such as hand tremor, sweating, convulsions, and delirium tremens\/hallucinations were more common in the\n ADH1B*1\/*1<\/jats:italic>\n group. The\n ADH1B*1\/*1<\/jats:italic>\n was positively associated with the ICD-10 criteria for \u2018tolerance\u2019 and \u2018withdrawal symptoms\u2019. The\n ADH1B*1\/*1<\/jats:italic>\n group and\n ALDH2*1\/*2<\/jats:italic>\n group had a larger ICD-10 score. Never flushing was reported by 91.7% and 35.2% of the\n ALDH2*1\/*1<\/jats:italic>\n and\n ALDH2*1\/*2<\/jats:italic>\n carriers, respectively. After a 1\u20132-year delay in the onset of habitual drinking in the former-\/current-flushing group, no differences in the ages of the aforementioned drinking milestones were found according to the flushing status.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n The\n ADH1B*1\/*1<\/jats:italic>\n and\n ALDH2*1\/*1<\/jats:italic>\n accelerated the development of drinking events and withdrawal symptoms in Japanese AD patients. ICD-10 score was larger in the\n ADH1B*1\/*1<\/jats:italic>\n group and\n ALDH2*1\/*2<\/jats:italic>\n group. The effects of alcohol flushing on drinking events were limited.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1097\/fpc.0000000000000528","type":"journal-article","created":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T06:16:51Z","timestamp":1710137811000},"page":"139-148","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":4,"title":["Associations of ADH1B and ALDH2 genotypes and alcohol flushing with drinking history, withdrawal symptoms, and ICD-10 criteria in Japanese alcohol-dependent men"],"prefix":"10.1097","volume":"34","author":[{"given":"Akira","family":"Yokoyama","sequence":"first","affiliation":[{"name":"Clinical Research Unit, National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Kanagawa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuji","family":"Yokoyama","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, National Institute of Public Health, Wako, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosuke","family":"Yumoto","sequence":"additional","affiliation":[{"name":"Departemt of Psychiatry, National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Kanagawa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuyoshi","family":"Takimura","sequence":"additional","affiliation":[{"name":"Departemt of Psychiatry, National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Kanagawa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomomi","family":"Toyama","sequence":"additional","affiliation":[{"name":"Departemt of Psychiatry, National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Kanagawa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junichi","family":"Yoneda","sequence":"additional","affiliation":[{"name":"Departemt of Psychiatry, National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Kanagawa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kotaro","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Departemt of Psychiatry, National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Kanagawa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruriko","family":"Minobe","sequence":"additional","affiliation":[{"name":"Departemt of Psychiatry, National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Kanagawa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanobu","family":"Matsuzaki","sequence":"additional","affiliation":[{"name":"Departemt of Psychiatry, National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Kanagawa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuru","family":"Kimura","sequence":"additional","affiliation":[{"name":"Departemt of Psychiatry, National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Kanagawa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachio","family":"Matsushita","sequence":"additional","affiliation":[{"name":"Departemt of Psychiatry, National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Kanagawa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2024,3,11]]},"reference":[{"key":"R1-20250808","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1086\/521201","article-title":"Geographically separate increases in the frequency of the derived ADH1B*47His allele in eastern and western Asia.","volume":"81","author":"Li","year":"2007","journal-title":"Am J Hum Genet"},{"key":"R2-20250808","doi-asserted-by":"crossref","first-page":"e0255276","DOI":"10.1371\/journal.pone.0255276","article-title":"Combinations of alcohol-induced flushing with genetic polymorphisms of alcohol and aldehyde dehydrogenases and the risk of alcohol dependence in Japanese men and women.","volume":"16","author":"Yokoyama","year":"2021","journal-title":"PLoS One"},{"key":"R3-20250808","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1111\/j.1469-1809.2009.00517.x","article-title":"Refined geographic distribution of the Oriental ALDH2*504Lys (nee 487Lys) variant.","volume":"73","author":"Li","year":"2009","journal-title":"Ann Hum Genet"},{"key":"R4-20250808","first-page":"677","article-title":"Alcohol and aldehyde dehydrogenase genotypes and alcoholism in Chinese men.","volume":"48","author":"Thomasson","year":"1991","journal-title":"Am J Hum Genet"},{"key":"R5-20250808","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1176\/ajp.152.8.1219","article-title":"Alcohol and aldehyde dehydrogenase polymorphism and the risk for alcoholism.","volume":"152","author":"Higuchi","year":"1995","journal-title":"Am J 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esophageal squamous cell carcinoma in Japanese men.","volume":"12","author":"Yokoyama","year":"2003","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"R10-20250808","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1158\/1055-9965.EPI-05-0911","article-title":"Alcohol dehydrogenase 2 His47Arg polymorphism influences drinking habit independently of aldehyde dehydrogenase 2 Glu487Lys polymorphism: analysis of 2,299 Japanese subjects.","volume":"15","author":"Matsuo","year":"2006","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"R11-20250808","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1111\/j.1530-0277.2011.01458.x","article-title":"ALDH2 and ADH1B interactions in retrospective reports of low-dose reactions and initial sensitivity to alcohol in Asian American college students.","volume":"35","author":"Luczak","year":"2011","journal-title":"Alcohol Clin Exp Res"},{"key":"R12-20250808","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1097\/FPC.0000000000000395","article-title":"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.","volume":"30","author":"Yokoyama","year":"2020","journal-title":"Pharmacogenet Genomics"},{"key":"R13-20250808","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1111\/j.1530-0277.2010.01202.x","article-title":"Polymorphisms of alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 and the blood and salivary ethanol and acetaldehyde concentrations of Japanese alcoholic men.","volume":"34","author":"Yokoyama","year":"2010","journal-title":"Alcohol Clin Exp Res"},{"key":"R14-20250808","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1093\/alcalc\/agt136","article-title":"Blood ethanol levels of nonabstinent Japanese alcoholic men in the morning after drinking and their ADH1B and ALDH2 genotypes.","volume":"49","author":"Yokoyama","year":"2014","journal-title":"Alcohol Alcohol"},{"key":"R15-20250808","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1016\/S0140-6736(81)91172-7","article-title":"Aldehyde dehydrogenase deficiency as cause of facial flushing reaction to alcohol in Japanese.","volume":"2","author":"Harada","year":"1981","journal-title":"Lancet"},{"key":"R16-20250808","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1111\/j.1530-0277.1989.tb00317.x","article-title":"Ethanol patch test: a simple and sensitive method for identifying ALDH phenotype.","volume":"13","author":"Muramatsu","year":"1989","journal-title":"Alcohol Clin Exp Res"},{"key":"R17-20250808","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1111\/j.1530-0277.1998.tb03928.x","article-title":"Development of a questionnaire method to discriminate between typical and atypical genotypes of low Km aldehyde dehydrogenase in a Japanese 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Japan.","volume":"2","author":"Harada","year":"1982","journal-title":"Lancet"},{"key":"R21-20250808","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1093\/alcalc\/agw002","article-title":"Prevalence and trends in alcohol dependence and alcohol use disorders in Japanese adults; Results from periodical nationwide surveys.","volume":"51","author":"Osaki","year":"2016","journal-title":"Alcohol Alcohol"},{"key":"R22-20250808","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1111\/j.1530-0277.1996.tb01152.x","article-title":"DSM-IV, DSM-III-R, and ICD-10 alcohol and drug abuse\/harmful use and dependence, United States, 1992: a nosological comparison.","volume":"20","author":"Grant","year":"1996","journal-title":"Alcohol Clin Exp Res"},{"key":"R23-20250808","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1111\/j.1530-0277.2002.tb02673.x","article-title":"Alcohol dependence symptoms and alcohol dehydrogenase 2 polymorphism: Israeli Ashkenazis, Sephardics, and recent Russian immigrants.","volume":"26","author":"Hasin","year":"2002","journal-title":"Alcohol Clin Exp Res"},{"key":"R24-20250808","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1093\/hmg\/ddn372","article-title":"Associations of ADH and ALDH2 gene variation with self report alcohol reactions, consumption and dependence: an integrated analysis.","volume":"18","author":"Macgregor","year":"2009","journal-title":"Hum Mol Genet"},{"key":"R25-20250808","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/mp.2011.124","article-title":"ADH1B is associated with alcohol dependence and alcohol consumption in populations of European and African ancestry.","volume":"17","author":"Bierut","year":"2012","journal-title":"Mol Psychiatry"},{"key":"R26-20250808","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1111\/adb.12244","article-title":"Which alcohol use disorder criteria contribute to the association of ADH1B with alcohol dependence?","volume":"21","author":"Hart","year":"2016","journal-title":"Addict Biol"},{"key":"R27-20250808","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1111\/j.1530-0277.1998.tb03683.x","article-title":"Clinical characteristics and disease course of alcoholics with inactive aldehyde dehydrogenase-2.","volume":"22","author":"Murayama","year":"1998","journal-title":"Alcohol Clin Exp Res"},{"key":"R28-20250808","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1037\/0021-843X.114.3.456","article-title":"Genetic associations of alcohol dehydrogenase with alcohol use disorders and endophenotypes in white college students.","volume":"114","author":"Wall","year":"2005","journal-title":"J Abnorm Psychol"},{"key":"R29-20250808","first-page":"707","article-title":"Involvement of genetic polymorphism of alcohol and aldehyde dehydrogenase in individual variation of alcohol metabolism.","volume":"29","author":"Mizoi","year":"1994","journal-title":"Alcohol Alcohol"},{"key":"R30-20250808","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1097\/FPC.0b013e3282609e67","article-title":"Pharmacokinetic and pharmacodynamic basis for partial protection against alcoholism in Asians, heterozygous for the variant ALDH2*2 gene allele.","volume":"17","author":"Peng","year":"2007","journal-title":"Pharmacogenet Genomics"},{"key":"R31-20250808","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1097\/FPC.0b013e32832ecf2e","article-title":"Pharmacokinetic and pharmacodynamic basis for overcoming acetaldehyde-induced adverse reaction in Asian alcoholics, heterozygous for the variant ALDH2*2 gene allele.","volume":"19","author":"Chen","year":"2009","journal-title":"Pharmacogenet Genomics"},{"key":"R32-20250808","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1097\/01.ALC.0000108667.79219.4D","article-title":"Alcohol dehydrogenases polymorphisms influence alcohol-elimination rates in a male Jewish population.","volume":"28","author":"Neumark","year":"2004","journal-title":"Alcohol Clin Exp Res"},{"key":"R33-20250808","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1111\/acer.13073","article-title":"Effects of ADH1B and ALDH2 genetic polymorphisms on alcohol elimination rates and salivary acetaldehyde levels in intoxicated Japanese alcoholic men.","volume":"40","author":"Yokoyama","year":"2016","journal-title":"Alcohol Clin Exp Res"},{"key":"R34-20250808","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1111\/j.1556-4029.2006.00161.x","article-title":"The association of alcohol-induced blackouts and grayouts to blood alcohol concentrations.","volume":"51","author":"Perry","year":"2006","journal-title":"J Forensic Sci"},{"key":"R35-20250808","doi-asserted-by":"crossref","first-page":"349","DOI":"10.15288\/jsa.2006.67.349","article-title":"ALDH2*2 is associated with a decreased likelihood of alcohol-induced blackouts in Asian American college students.","volume":"67","author":"Luczak","year":"2006","journal-title":"J Stud Alcohol"},{"key":"R36-20250808","first-page":"13","article-title":"Neurochemical mechanisms underlying alcohol withdrawal.","volume":"22","author":"Littleton","year":"1998","journal-title":"Alcohol Health Res World"},{"key":"R37-20250808","first-page":"25","article-title":"Kindling in alcohol withdrawal.","volume":"22","author":"Becker","year":"1998","journal-title":"Alcohol Health Res World"},{"key":"R38-20250808","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1111\/hepr.13475","article-title":"Associations among liver disease, serum lipid profile, body mass index, ketonuria, meal skipping, and the alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 genotypes in Japanese men with alcohol dependence.","volume":"50","author":"Yokoyama","year":"2020","journal-title":"Hepatol Res"},{"issue":"Suppl 5","key":"R39-20250808","doi-asserted-by":"crossref","first-page":"15S","DOI":"10.1111\/j.1530-0277.2001.tb02369.x","article-title":"The role of acetaldehyde in the action of alcohol (Update 2000).","volume":"25","author":"Eriksson","year":"2001","journal-title":"Alcohol Clin Exp Res"},{"key":"R40-20250808","first-page":"258","article-title":"Role of acetaldehyde in mediating the pharmacological and behavioral effects of alcohol.","volume":"29","author":"Quertemont","year":"2006","journal-title":"Alcohol Res Health"},{"key":"R41-20250808","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1093\/alcalc\/agz011","article-title":"Meta-analysis on associations of alcohol metabolism genes with alcohol use disorder in East Asians.","volume":"54","author":"Zaso","year":"2019","journal-title":"Alcohol Alcohol"},{"key":"R42-20250808","doi-asserted-by":"crossref","first-page":"5847","DOI":"10.1021\/bi00319a026","article-title":"Human liver alcohol dehydrogenase: purification and kinetic characterization of the \u03b22\u03b22, \u03b22\u03b21, \u03b1\u03b22 and \u03b22\u03b31 \u2018oriental\u2019 isozymes.","volume":"23","author":"Yin","year":"1984","journal-title":"Biochemistry"},{"key":"R43-20250808","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1097\/FPC.0000000000000205","article-title":"Ethanol-metabolizing activities and isozyme protein contents of alcohol and aldehyde dehydrogenases in human liver: phenotypic traits of the ADH1B*2 and ALDH2*2 variant gene alleles.","volume":"26","author":"Chiang","year":"2016","journal-title":"Pharmacogenet Genomics"}],"container-title":["Pharmacogenetics and 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