title: Genetic variants in or near ADH1B and ADH1C affect susceptibility to alcohol dependence in a British and Irish population.
abstract: Certain single nucleotide polymorphisms (SNPs) in genes encoding alcohol dehydrogenase (ADH) enzymes confer a significant protective effect against alcohol dependence syndrome (ADS) in East Asian populations. Recently, attention has focused on the role of these SNPs in determining ADS risk in European populations. To further elucidate these associations, SNPs of interest in ADH1B, ADH1C and the ADH1B/1C intergenic region were genotyped in a British and Irish population (ADS cases n = 1076: controls n = 1027) to assess their relative contribution to ADS risk. A highly significant, protective association was observed between the minor allele of rs1229984 in ADH1B and ADS risk [allelic P = 8.4 × 10(-6) , odds ratio (OR) = 0.26, 95 percent confidence interval, 0.14, 0.49]. Significant associations were also observed between ADS risk and the ADH1B/1C intergenic variant, rs1789891 [allelic P = 7.2 × 10(-5) , OR = 1.4 (1.2, 1.6)] and three non-synonymous SNPs rs698, rs1693482 and rs283413 in ADH1C. However, these associations were not completely independent; thus, while the ADH1B rs1229984 minor allele association was independent of those of the intergenic variant rs1789891 and the three ADH1C variants, the three ADH1C variants were not individually independent. In conclusion, the rare ADH1B rs1229984 mutation provides significant protection against ADS in this British and Irish population; other variants in the ADH gene cluster also alter ADS risk, although the strong linkage disequilibrium between SNPs at this location precluded clear identification of the variant(s) driving the associations.
authors.affiliation: Molecular Psychiatry Laboratory, Mental Health Sciences Unit, Faculty of Brain Sciences, University College London, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Way
authors.forename: Andrew
authors.initials: A
authors.lastname: McQuillin
authors.forename: Jit
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authors.lastname: Saini
authors.forename: Kush
authors.initials: K
authors.lastname: Ruparelia
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Lydall
authors.forename: Irene
authors.initials: I
authors.lastname: Guerrini
authors.forename: David
authors.initials: D
authors.lastname: Ball
authors.forename: Iain
authors.initials: I
authors.lastname: Smith
authors.forename: Giorgia
authors.initials: G
authors.lastname: Quadri
authors.forename: Allan D
authors.initials: AD
authors.lastname: Thomson
authors.forename: Katherine
authors.initials: K
authors.lastname: Kasiakogia-Worlley
authors.forename: Raquin
authors.initials: R
authors.lastname: Cherian
authors.forename: Priyanthi
authors.initials: P
authors.lastname: Gunwardena
authors.forename: Harish
authors.initials: H
authors.lastname: Rao
authors.forename: Girija
authors.initials: G
authors.lastname: Kottalgi
authors.forename: Shamir
authors.initials: S
authors.lastname: Patel
authors.forename: Audrey
authors.initials: A
authors.lastname: Hillman
authors.forename: Ewen
authors.initials: E
authors.lastname: Douglas
authors.forename: Sherhzad Y
authors.initials: SY
authors.lastname: Qureshi
authors.forename: Gerry
authors.initials: G
authors.lastname: Reynolds
authors.forename: Sameer
authors.initials: S
authors.lastname: Jauhar
authors.forename: Aideen
authors.initials: A
authors.lastname: O'Kane
authors.forename: Alex
authors.initials: A
authors.lastname: Dedman
authors.forename: Sally
authors.initials: S
authors.lastname: Sharp
authors.forename: Radhika
authors.initials: R
authors.lastname: Kandaswamy
authors.forename: Karim
authors.initials: K
authors.lastname: Dar
authors.forename: David
authors.initials: D
authors.lastname: Curtis
authors.forename: Marsha Y
authors.initials: MY
authors.lastname: Morgan
authors.forename: Hugh M D
authors.initials: HM
authors.lastname: Gurling
mesh_terms: D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000437:Alcoholism / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007494:Ireland / Q000208:ethnology; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D006113:United Kingdom / Q000208:ethnology
chemical_list: C489332:ADH1B protein, human; C420272:ADH1C protein, human; D000426:Alcohol Dehydrogenase
keywords: Alcohol dehydrogenase; British and Irish ancestry; alcohol dependence; association study; population attributable risk; protective alleles