title: Association of alcohol dehydrogenase genes with alcohol-related phenotypes in a Native American community sample.
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.
authors.affiliation: Department of Psychological Sciences, University of Missouri, Columbia, Missouri, USA.
authors.forename: Ian R
authors.initials: IR
authors.lastname: Gizer
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Edenberg
authors.forename: David A
authors.initials: DA
authors.lastname: Gilder
authors.forename: Kirk C
authors.initials: KC
authors.lastname: Wilhelmsen
authors.forename: Cindy L
authors.initials: CL
authors.lastname: Ehlers
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D019973:Alcohol-Related Disorders / Q000208:ethnology / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014481:United States; D055815:Young Adult
chemical_list: C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase; C105552:alcohol dehydrogenase IV