title: Effects of ADH1B and ALDH2 Genetic Polymorphisms on Alcohol Elimination Rates and Salivary Acetaldehyde Levels in Intoxicated Japanese Alcoholic Men.
abstract: The genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) are associated with the risk of alcoholism and upper aerodigestive tract cancer in alcoholics. Salivary ethanol (sEtOH) levels are well correlated with blood EtOH levels.
  
  
  
  To study the effects of ADH1B and ALDH2 genotypes on the alcohol elimination rate (AER) and salivary acetaldehyde (sAcH) levels, we measured the sEtOH and sAcH levels twice at a 1-hour intervals in 99 intoxicated Japanese alcoholic men who had stopped drinking for 4 or more hours.
  
  
  
  The initial sEtOH levels did not differ between the ADH1B*2 group (n = 50) and the ADH1B*1/*1 group (n = 49) (median: 0.617 vs. 0.762 mg/ml). The salivary AER (sAER) increased as the sEtOH levels increased (p < 0.0001). After stratification according to the sEtOH levels (<0.4, 0.4 to 0.99, and ≥1.00 mg/ml), the median sAER of the ADH1B*2 group was 0.075, 0.188, and 0.228 mg/ml/h, respectively, and that of the ADH1B*1/*1 group was 0.037, 0.115, and 0.233 mg/ml/h, respectively. The sAER of the ADH1B*2 group was faster than that of the ADH1B*1/*1 group overall (p = 0.001) and when the sEtOH category was 0.4 to 0.99 mg/ml (p < 0.0001). The ADH1B genotype and the sEtOH levels had an interaction effect on the sAER (p = 0.036). A multiple linear regression analysis with a stepwise procedure selected the ADH1B*2 allele (p = 0.004) and the sEtOH levels (p < 0.0001) as positive predictors of sAER. The sAER did not differ according to the ALDH2 genotype. The sAcH levels were higher than the blood AcH levels reported in alcoholics, probably because of AcH production by oral microorganisms. The sAcH of the ALDH2*1/*2 group (n = 18) was higher than that of the ALDH2*1/*1 group (n = 81) overall (p = 0.0008) and when the corresponding sEtOH category was ≥1.00 mg/ml (median: 3.195 vs. 1.776 μg/ml, p = 0.009). A multiple linear regression analysis selected the ALDH2*1/*2 and the sEtOH levels as positive predictors of the sAcH levels (p < 0.0001).
  
  
  
  The enhanced AER in ADH1B*2 carriers and the increased sAcH levels in ALDH2*1/*2 carriers among intoxicated alcoholics provide possible mechanisms explaining how each genetic polymorphism affects the risk of alcoholism and upper aerodigestive tract cancer.
authors.affiliation: National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Kanagawa, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yokoyama
authors.affiliation: Suntory Business Expert Limited, Suntory World Research Center, Soraku-gun, Kyoto, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kamada
authors.affiliation: National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Kanagawa, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Imazeki
authors.affiliation: National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Kanagawa, Japan.
authors.forename: Emiko
authors.initials: E
authors.lastname: Hayashi
authors.affiliation: School of Pharmaceutical Science, Mukogawa Women's University, Nishinomiya, Hyogo, Japan.
authors.forename: Shigenori
authors.initials: S
authors.lastname: Murata
authors.affiliation: School of Pharmaceutical Science, Mukogawa Women's University, Nishinomiya, Hyogo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kinoshita
authors.affiliation: Department of Health Promotion, National Institute of Public Health, Wako, Saitama, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Yokoyama
authors.affiliation: Suntory Business Expert Limited, Suntory World Research Center, Soraku-gun, Kyoto, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kitagawa
mesh_terms: D000079:Acetaldehyde / Q000378:metabolism*; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000435:Alcoholic Intoxication / Q000235:genetics* / Q000378:metabolism*; D000071396:Aldehyde Dehydrogenase, Mitochondrial / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D000431:Ethanol / Q000378:metabolism*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D012463:Saliva / Q000378:metabolism*
chemical_list: D000431:Ethanol; C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase; C096127:ALDH2 protein, human; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000079:Acetaldehyde
keywords: Acetaldehyde; Alcohol Dehydrogenase; Alcoholism; Aldehyde Dehydrogenase; Ethanol Elimination; Saliva