Association of alcohol dehydrogenase genes with alcohol-related phenotypes in a Native American community sample

Alcohol Clin Exp Res. 2011 Nov;35(11):2008-18. doi: 10.1111/j.1530-0277.2011.01552.x. Epub 2011 Jun 2.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Alcohol Dehydrogenase / genetics*
  • Alcohol-Related Disorders / ethnology
  • Alcohol-Related Disorders / genetics*
  • Chromosomes, Human, Pair 4 / genetics
  • Female
  • Genotype
  • Haplotypes
  • Humans
  • Indians, North American / genetics*
  • Male
  • Middle Aged
  • Phenotype*
  • Polymorphism, Single Nucleotide / genetics
  • United States
  • Young Adult

Substances

  • ADH1B protein, human
  • Alcohol Dehydrogenase
  • alcohol dehydrogenase IV