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Home > Genetic variants in or near ADH1B and ADH1C affect susceptibility to alcohol dependence in a British and Irish population.

Way, Michael and McQuillin, Andrew and Saini, Jit and Ruparelia, Kush and Lydall, Gregory J and Guerrini, Irene and Ball, David and Smith, Iain and Quadri, Giorgia and Thomson, Allan D and Kasiakogia-Worlley, Katherine and Cherian, Raquin and Gunwardena, Priyanthi and Rao, Harish and Kottalgi, Girija and Patel, Shamir and Hillman, Audrey and Douglas, Ewen and Qureshi, Sherhzad Y and Reynolds, Gerry and Jauhar, Sameer and O'Kane, Aideen and Dedman, Alex and Sharp, Sally and Kandaswamy, Radhika and Dar, Karim and Curtis, David and Morgan, Marsha Y and Gurling, Hugh M D (2015) Genetic variants in or near ADH1B and ADH1C affect susceptibility to alcohol dependence in a British and Irish population. Addiction Biology , 20 , (3) , pp. 594-604. doi: 10.1111/adb.12141.

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.


Item Type
Article
Publication Type
Irish-related, International, Article
Drug Type
Alcohol
Date
2015
Identification #
doi: 10.1111/adb.12141
Page Range
pp. 594-604
Publisher
Wiley
Volume
20
Number
3
EndNote

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