title: Trends in gastrectomy and ADH1B and ALDH2 genotypes in Japanese alcoholic men and their gene-gastrectomy, gene-gene and gene-age interactions for risk of alcoholism.
abstract: OBJECTIVE
  The life-time drinking profiles of Japanese alcoholics have shown that gastrectomy increases susceptibility to alcoholism. We investigated the trends in gastrectomy and alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) genotypes and their interactions in alcoholics.
  
  
  METHODS
  This survey was conducted on 4879 Japanese alcoholic men 40 years of age or older who underwent routine gastrointestinal endoscopic screening during the period 1996-2010. ADH1B/ALDH2 genotyping was performed in 3702 patients.
  
  
  RESULTS
  A history of gastrectomy was found in 508 (10.4%) patients. The reason for the gastrectomy was peptic ulcer in 317 patients and gastric cancer in 187 patients. The frequency of gastrectomy had gradually decreased from 13.3% in 1996-2000 to 10.5% in 2001-2005 and to 7.8% in 2006-2010 (P < 0.0001). ADH1B*1/*1 was less frequent in the gastrectomy group than in the non-gastrectomy group (age-adjusted prevalence: 20.4 vs. 27.6%, P = 0.006). ALDH2 genotype distribution did not differ between the two groups. The frequency of inactive ALDH2*1/*2 heterozygotes increased slightly from 13.0% in 1996-2000 to 14.0% in 2001-2005 and to 15.4% in 2006-2010 (P < 0.08). Two alcoholism-susceptibility genotypes, ADH1B*1/*1 and ALDH2*1/*1, modestly but significantly tended not to occur in the same individual (P = 0.026). The frequency of ADH1B*1/*1 decreased with ascending age groups.
  
  
  CONCLUSIONS
  The high frequency of history of gastrectomy suggested that gastrectomy is still a risk factor for alcoholism, although the percentage decreased during the period. The alcoholism-susceptibility genotype ADH1B*1/*1 was less frequent in the gastrectomy group, suggesting a competitive gene-gastrectomy interaction for alcoholism. A gene-gene interaction and gene-age interactions regarding the ADH1B genotype were observed.
authors.affiliation: National Hospital Organization Kurihama Medical and Addiction Center, 5-3-1 Nobi, Yokosuka, Kanagawa 239-0841, Japan. a_yokoyama@kurihama1.hosp.go.jp
authors.forename: Akira
authors.initials: A
authors.lastname: Yokoyama
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Matsui
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mizukami
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kimura
authors.forename: Sachio
authors.initials: S
authors.lastname: Matsushita
authors.forename: Susumu
authors.initials: S
authors.lastname: Higuchi
authors.forename: Katsuya
authors.initials: K
authors.lastname: Maruyama
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D057229:Alcoholics; D000437:Alcoholism / Q000208:ethnology / Q000235:genetics*; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D044466:Asian People / Q000208:ethnology / Q000235:genetics*; D003430:Cross-Sectional Studies / Q000639:trends; D004843:Epistasis, Genetic / Q000235:genetics*; D005260:Female; D005743:Gastrectomy / Q000639:trends*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial