Association of Alcohol Dehydrogenase Genes with Alcohol-Related Phenotypes in a Native American Community Sample

Department of Psychological Sciences, University of Missouri, Columbia, Missouri, USA.
Alcoholism Clinical and Experimental Research (Impact Factor: 3.21). 06/2011; 35(11):2008-18. DOI: 10.1111/j.1530-0277.2011.01552.x
Source: PubMed


Previous linkage studies, including a study of the Native American population described in the present report, have provided evidence for linkage of alcohol dependence and related traits to chromosome 4q near a cluster of alcohol dehydrogenase (ADH) genes, which encode enzymes of alcohol metabolism.
The present study tested for associations between alcohol dependence and related traits and 22 single-nucleotide polymorphisms (SNPs) spanning the 7 ADH genes. Participants included 586 adult men and women recruited from 8 contiguous Native American reservations. A structured interview was used to assess DSM-III-R alcohol dependence criteria as well as a set of severe alcohol misuse symptoms and alcohol withdrawal symptoms.
No evidence for association with the alcohol dependence diagnosis was observed, but an SNP in exon 9 of ADH1B (rs2066702; ADH1B*3) and an SNP at the 5' end of ADH4 (rs3762894) showed significant evidence of association with the presence of withdrawal symptoms (p = 0.0018 and 0.0012, respectively). Further, a haplotype analysis of these 2 SNPs suggested that the haplotypes containing either of the minor alleles were protective against alcohol withdrawal relative to the ancestral haplotype (p = 0.000006).
These results suggest that variants in the ADH1B and ADH4 genes may be protective against the development of some symptoms associated with alcohol dependence.

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