title: Association of the aldehyde dehydrogenase 2 promoter polymorphism with alcohol consumption and reactions in an American Jewish population.
abstract: BACKGROUND
  Reduction in activity of the mitochondrial aldehyde dehydrogenase 2 (ALDH2) enzyme due to genetic deficiency causes reactions related to alcohol consumption and lowers the risk of alcoholism. ALDH2*2 is the only functionally significant polymorphism of the ALDH2 gene. An additional polymorphic locus in the promoter (G to A substitution approximately 360 bp from the translation start site) may influence ALDH2 activity through effects on transcriptional activity. The A allele is predicted to be less active transcriptionally than the G allele. Therefore, we hypothesized that individuals with 1 or 2 A alleles would have exaggerated reactions to alcohol.
  
  
  METHODS
  Fifty-three Jewish college students from a Midwestern University and 76 Jewish individuals living in a large Midwestern city (all of Ashkenazi descent) were tested for associations between ALDH2*G and ALDH2*A alleles and self-reported alcohol consumption and responses to alcohol. Genotype determination was performed using PCR and slot-blot hybridization. As alcohol drinking behavior differed substantially between the college students and the general population, as well as between males and females, the analyses were performed separately in each group.
  
  
  RESULTS
  The frequency of the ALDH2*A allele was 0.87 in the 129 Jewish individuals tested. Among the general Jewish population, those who were homozygous for ALDH2*A drank fewer drinks per occasion than individuals who were not homozygous for the ALDH2*A allele, but did not drink significantly less frequently. When the other covariates (ADH1B genotype, gender, and population) were controlled for, there was a marginal association between ALDH2A genotype and quantity of alcohol consumed and the number of drinks consumed before feeling drowsy.
  
  
  CONCLUSIONS
  This study suggests that the ALDH2*A allele status may correlate with variations in alcohol consumption patterns among Jews, independent of the effect of ADH1B genotype.
authors.affiliation: Department of Medicine, Indiana University School of Medicine and the Richard Roudebush Veteran's Affairs Medical Center, Indianapolis, Indiana, USA.
authors.forename: Monika
authors.initials: M
authors.lastname: Fischer
authors.forename: Leah Flury
authors.initials: LF
authors.lastname: Wetherill
authors.forename: Lucinda G
authors.initials: LG
authors.lastname: Carr
authors.forename: Min
authors.initials: M
authors.lastname: You
authors.forename: David W
authors.initials: DW
authors.lastname: Crabb
mesh_terms: D000293:Adolescent; D000328:Adult; D000426:Alcohol Dehydrogenase / Q000235:genetics; D000428:Alcohol Drinking / Q000208:ethnology* / Q000235:genetics*; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006306:Health Surveys; D006801:Humans; D007585:Jews / Q000208:ethnology* / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D014481:United States
chemical_list: C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial