Association of alcohol dehydrogenase genes with alcohol-related phenotypes in a native american community sample

Ian R. Gizer, Howard J. Edenberg, David A. Gilder, Kirk C. Wilhelmsen, Cindy L. Ehlers

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Abstract

Background: 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. Methods: 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. Results: 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). Conclusions: These results suggest that variants in the ADH1B and ADH4 genes may be protective against the development of some symptoms associated with alcohol dependence.

Original languageEnglish (US)
Pages (from-to)2008-2018
Number of pages11
JournalAlcoholism: Clinical and Experimental Research
Volume35
Issue number11
DOIs
StatePublished - Nov 1 2011

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Keywords

  • Alcohol dehydrogenase
  • Alcohol dependence
  • Alcohol withdrawal
  • Candidate gene analysis
  • Genetic association

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Psychiatry and Mental health
  • Toxicology

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