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Genetic variants in or near ADH 1 B and ADH 1 C affect susceptibility to alcohol dependence in a B ritish and I rish population
Author(s) -
Way Michael,
McQuillin Andrew,
Saini Jit,
Ruparelia Kush,
Lydall Gregory J.,
Guerrini Irene,
Ball David,
Smith Iain,
Quadri Giorgia,
Thomson Allan D.,
KasiakogiaWorlley Katherine,
Cherian Raquin,
Gunwardena Priyanthi,
Rao Harish,
Kottalgi Girija,
Patel Shamir,
Hillman Audrey,
Douglas Ewen,
Qureshi Sherhzad Y.,
Reynolds Gerry,
Jauhar Sameer,
O'Kane Aideen,
Dedman Alex,
Sharp Sally,
Kandaswamy Radhika,
Dar Karim,
Curtis David,
Morgan Marsha Y.,
Gurling Hugh M. D.
Publication year - 2015
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/adb.12141
Subject(s) - adh1b , single nucleotide polymorphism , genetics , odds ratio , linkage disequilibrium , minor allele frequency , allele , population , biology , genotype , medicine , gene , dehydrogenase , environmental health , enzyme , branched chain alpha keto acid dehydrogenase complex , biochemistry
Certain single nucleotide polymorphisms ( SNPs ) in genes encoding alcohol dehydrogenase ( ADH ) enzymes confer a significant protective effect against alcohol dependence syndrome ( ADS ) in East A sian populations. Recently, attention has focused on the role of these SNPs in determining ADS risk in E uropean populations. To further elucidate these associations, SNPs of interest in ADH 1 B , ADH 1 C and the ADH 1 B /1 C intergenic region were genotyped in a B ritish and I rish 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 rs 1229984 in ADH 1 B 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 ADH 1 B /1 C intergenic variant, rs 1789891 [allelic P = 7.2 × 10 −5 , OR = 1.4 (1.2, 1.6)] and three non‐synonymous SNPs rs 698, rs 1693482 and rs 283413 in ADH 1 C . However, these associations were not completely independent; thus, while the ADH 1 B rs 1229984 minor allele association was independent of those of the intergenic variant rs 1789891 and the three ADH 1 C variants, the three ADH 1 C variants were not individually independent. In conclusion, the rare ADH 1 B rs 1229984 mutation provides significant protection against ADS in this B ritish and I rish 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.