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Association of Alcohol Dehydrogenase Genes with Alcohol‐Related Phenotypes in a Native American Community Sample
Author(s) -
Gizer Ian R.,
Edenberg Howard J.,
Gilder David A.,
Wilhelmsen Kirk C.,
Ehlers Cindy L.
Publication year - 2011
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2011.01552.x
Subject(s) - adh1b , single nucleotide polymorphism , snp , haplotype , alcohol dependence , genetics , alcohol dehydrogenase , genetic association , candidate gene , biology , alcohol , allele , gene , medicine , genotype , enzyme , dehydrogenase , branched chain alpha keto acid dehydrogenase complex , biochemistry
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 = 0.6). 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.