title: Platelet Counts and Genetic Polymorphisms of Alcohol Dehydrogenase-1B and Aldehyde Dehydrogenase-2 in Japanese Alcoholic Men.
abstract: Thrombocytopenia during intoxication, rebound thrombocytosis during 1 to 3 weeks of abstinence, and subsequent normalization of the platelet count are common in alcoholics.
  
  
  
  We evaluated 989 Japanese alcoholic men to identify the effects of genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B; rs1229984) and aldehyde dehydrogenase-2 (ALDH2; rs671) on platelet counts during an 8-week in-hospital abstinence period.
  
  
  
  Thrombocytopenia (<15 × 104/μl) was observed in 25.9% of the subjects upon admission. The platelet counts increased from 21.4 ± 0.3 × 104/μl (mean ± SE) to 27.6 ± 0.3 × 104/μl, and a rebound platelet increase of  ≥10 × 104/μl was observed in 28.6% of the patients during the first 2 weeks after admission. By 4 weeks, the mean platelet counts had returned to intermediate levels and remained stable thereafter. The reversible suppression and rebound increase in the platelet counts were more prominent in the slow-metabolizing ADH1B*1/*1 group than in the fast-metabolizing ADH1B*2 group. Throughout the 8 weeks, the mean platelet counts of the active ALDH2*1/*1 group were consistently lower than those in the inactive ALDH2*1/*2 group. Cirrhosis was a strong determinant of a lower platelet count. After adjustments for nongenetic factors including cirrhosis, multiple linear regression analyses showed that the ADH1B*1/*1 genotype was associated with a lower platelet count (partial regression coefficient = -1.3 × 104/μl) on the admission day, but subsequently had a positive effect on the platelet count at 1 and 2 weeks after admission (+1.5 and +3.8 × 104/μl, respectively). The ALDH2*1/*1 genotype was associated with a lower platelet count (-2.1 to -3.9 × 104/μl) consistently throughout the 8 weeks. Multiple logistic regression analyses showed that the ADH1B*1/*1 genotype increased the risk of thrombocytopenia upon admission (odds ratio [95% confidence interval] = 1.61 [1.14 to 2.27]) and of a rebound platelet increase during the first 2 weeks (3.86 [2.79 to 5.34]). The ALDH2*1/*1 genotype increased the risk of thrombocytopenia upon admission (1.73 [1.06 to 2.82]).
  
  
  
  In alcoholics, the ADH1B*1/*1 genotype increased the risk of thrombocytopenia upon admission and of a rebound platelet increase 2 weeks thereafter, while the ALDH2*1/*1 genotype was associated with lower platelet counts throughout the 8-week hospital stay.
authors.affiliation: National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Kanagawa, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yokoyama
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: National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Kanagawa, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mizukami
authors.affiliation: National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Kanagawa, Japan.|Department of Geriatric Medicine, Kyorin University Hospital, Mitaka, Tokyo, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Matsui
authors.affiliation: National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Kanagawa, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kimura
authors.affiliation: National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Kanagawa, Japan.
authors.forename: Sachio
authors.initials: S
authors.lastname: Matsushita
authors.affiliation: National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Kanagawa, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Higuchi
authors.affiliation: National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Kanagawa, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Maruyama
mesh_terms: D000368:Aged; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000437:Alcoholism / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D010976:Platelet Count / Q000379:methods; D011110:Polymorphism, Genetic / Q000235:genetics*; D013921:Thrombocytopenia / Q000097:blood / Q000175:diagnosis / Q000235:genetics
chemical_list: D005819:Genetic Markers; C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase; C096127:ALDH2 protein, human; D000071396:Aldehyde Dehydrogenase, Mitochondrial
keywords: Alcohol Dehydrogenase-1B; Aldehyde Dehydrogenase-2; Liver Disease; Platelet; Thrombocytopenia