title: Genetic variation in alcohol metabolizing enzymes among Inuit and its relation to drinking patterns.
abstract: BACKGROUND
  Variation in genes involved in alcohol metabolism is associated with drinking patterns worldwide. We compared variation in these genes among the Inuit with published results from the general population of Denmark and, due to the Asian ancestry of the Inuit, with Han Chinese. We analyzed the association between gene variations and drinking patterns among the Inuit.
  
  
  METHODS
  We genotyped 4162 Inuit participants from two population health surveys. Information on drinking patterns was available for 3560. Seven single nucleotide polymorphisms (SNPs) were examined: ADH1B arg48his, ADH1C ile350val, ADH1C arg272gln, ALDH2 glu504lys, ALDH2 5'-UTR A-357G, ALDH1B1 ala86val and ALDH1B1 arg107leu.
  
  
  RESULTS
  The allele distribution differed significantly between Inuit and the general population of Denmark. A protective effect on heavy drinking was found for the TT genotype of the ALDH1B1 arg107leu SNP (OR=0.59; 95% CI 0.37-0.92), present in 3% of pure Inuit and 37% of Danes. The ADH1C GG genotype was associated with heavy drinking and a positive CAGE test (OR 1.34; 95% CI 1.05-1.72). It was present in 27% of Inuit and 18% of Danes. The Asian genotype pattern with a high frequency of the ADH1B A allele and an ALDH2 gene coding for an inactive enzyme was not present in Greenland.
  
  
  CONCLUSIONS
  ADH1C and ALDH1B1 arg107leu SNPs play a role in the shaping of drinking patterns among the Inuit in Greenland. A low frequency of the ALDH1B1 arg107leu TT genotype compared with the general population in Denmark deserves further study. This genotype was protective of heavy drinking among the Inuit.
authors.affiliation: National Institute of Public Health, University of Southern Denmark, Øster Farimagsgade 5A, 1353 Copenhagen K, Denmark; Greenland Centre for Health Research, University of Greenland, 3900 Nuuk, Greenland. Electronic address: pb@niph.dk.
authors.forename: Peter
authors.initials: P
authors.lastname: Bjerregaard
authors.affiliation: National Institute of Public Health, University of Southern Denmark, Øster Farimagsgade 5A, 1353 Copenhagen K, Denmark.
authors.forename: Stine Schou
authors.initials: SS
authors.lastname: Mikkelsen
authors.affiliation: National Institute of Public Health, University of Southern Denmark, Øster Farimagsgade 5A, 1353 Copenhagen K, Denmark; Gastrounit, Medical Division, Copenhagen University Hospital Hvidovre, Kettegård Alle 30, 2650 Hvidovre, Denmark.
authors.forename: Ulrik
authors.initials: U
authors.lastname: Becker
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Universitetsparken 1, 2100 Copenhagen, Denmark.
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
authors.affiliation: National Institute of Public Health, University of Southern Denmark, Øster Farimagsgade 5A, 1353 Copenhagen K, Denmark.
authors.forename: Janne S
authors.initials: JS
authors.lastname: Tolstrup
mesh_terms: D000328:Adult; D000426:Alcohol Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D000428:Alcohol Drinking / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D000080924:Aldehyde Dehydrogenase 1 Family; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D003718:Denmark / Q000208:ethnology; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006116:Greenland / Q000208:ethnology; D006306:Health Surveys / Q000379:methods; D006801:Humans; D004930:Inuit / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: C420272:ADH1C protein, human; D000426:Alcohol Dehydrogenase; D000080924:Aldehyde Dehydrogenase 1 Family; C524846:ALDH1B1 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial
keywords: Alcohol; Genetics; Greenland; Inuit