Genetic variants in or near ADH 1 B and ADH 1 C affect susceptibility to alcohol dependence in a British and Irish population

作者：Michael Way, Andrew McQuillin, Jit Saini, Kush Ruparelia, Gregory Lydall, Irene Guerrini, David Ball, Iain Smith, Giorgia Quadri, Allan D. Thomson, Katherine Kasiakogia-Worlley, Raquin Cherian, Priyanthi Gunwardena, H. Shanker Rao, Girija Kottalgi, Shamir Patel, Audrey Hillman, Ewen Douglas, Sherhzad Yameen Qureshi, Gerry Reynolds, Sameer Jauhar, Aideen O’Kane, Alex Dedman, Sally I. Sharp, Radhika Kandaswamy, Karim Dar, David Curtis, Marsha Y. Morgan, Hugh Gurling · 发表于：Addiction Biology · 年份：2014 · DOI：10.1111/adb.12141 · 被引用次数：28 · 研究领域：Alcohol Consumption and Health Effects、Substance Abuse Treatment and Outcomes、Peroxisome Proliferator-Activated Receptors

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 diseq...