title: Genetic determinants of both ethanol and acetaldehyde metabolism influence alcohol hypersensitivity and drinking behaviour among Scandinavians.
abstract: BACKGROUND
  Although hypersensitivity reactions following intake of alcoholic drinks are common in Caucasians, the underlying mechanisms and clinical significance are not known. In contrast, in Asians, alcohol-induced asthma and flushing have been shown to be because of a single nucleotide polymorphism (SNP), the acetaldehyde dehydrogenase 2 (ALDH2) 487lys, causing decreased acetaldehyde (the metabolite of ethanol) metabolism and high levels of histamine. However, the ALDH2 487lys is absent in Caucasians.
  
  
  OBJECTIVE
  To investigate the genetic determinants of self-reported alcohol-induced hypersensitivity reactions in Caucasians.
  
  
  METHODS
  The study included two population-based studies of 1216 and 6784 adults living in Copenhagen. Assessment of alcohol consumption and hypersensitivity reactions (in a subgroup) was performed by a questionnaire and was related to common SNPs of genes encoding alcohol dehydrogenases (ADHs) and ALDHs.
  
  
  RESULTS
  In both populations, alcohol drinkers with a genetically determined fast metabolism of ethanol (the A allele of the ADH1b rs1229984) had an increased risk of alcohol-induced hypersensitivity reactions (odds ratio AA/AG vs. GG in combined populations: 1.82, 95% CI 1.04-3.17). In both populations, a common SNP encoding ALDH1b1 (rs2228093) was found to be significantly associated with alcohol-induced hypersensitivity (odds ratio TT vs. CC in combined populations: 2.53, 95% CI 1.31-4.90).
  
  
  CONCLUSIONS
  Our data support that alcohol sensitivity in Caucasians is genetically determined and suggest that a histamine-releasing effect of acetaldehyde represents a plausible biological mechanism. Furthermore, we present the first report of a clinically significant SNP within the acetaldehyde-metabolizing system in a Caucasian population.
authors.affiliation: Research Centre for Prevention and Health, The Capital Region of Denmark, Glostrup University Hospital, Glostrup, Denmark. alli@glo.regionh.dk
authors.forename: A
authors.initials: A
authors.lastname: Linneberg
authors.forename: A
authors.initials: A
authors.lastname: Gonzalez-Quintela
authors.forename: C
authors.initials: C
authors.lastname: Vidal
authors.forename: T
authors.initials: T
authors.lastname: Jørgensen
authors.forename: M
authors.initials: M
authors.lastname: Fenger
authors.forename: T
authors.initials: T
authors.lastname: Hansen
authors.forename: O
authors.initials: O
authors.lastname: Pedersen
authors.forename: L L N
authors.initials: LL
authors.lastname: Husemoen
mesh_terms: D000079:Acetaldehyde / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000434:Alcoholic Beverages / Q000009:adverse effects*; D000437:Alcoholism / Q000201:enzymology*; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000080924:Aldehyde Dehydrogenase 1 Family; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000483:Alleles; D003718:Denmark; D004342:Drug Hypersensitivity / Q000235:genetics*; D000431:Ethanol / Q000009:adverse effects* / Q000378:metabolism / Q000494:pharmacology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D044465:White People
chemical_list: D000431:Ethanol; D000080924:Aldehyde Dehydrogenase 1 Family; C524846:ALDH1B1 protein, human; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000079:Acetaldehyde