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.
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: E Borràs; C Coutelle; A Rosell; F Fernández-Muixi; M Broch; B Crosas; L Hjelmqvist; A Lorenzo; C Gutiérrez; M Santos; M Szczepanek; M Heilig; P Quattrocchi; J Farrés; F Vidal; C Richart; T Mach; J Bogdal; H Jörnvall; H K Seitz; P Couzigou; X Parés Journal: Hepatology Date: 2000-04 Impact factor: 17.425
Authors: N L Saccone; J M Kwon; J Corbett; A Goate; N Rochberg; H J Edenberg; T Foroud; T K Li; H Begleiter; T Reich; J P Rice Journal: Am J Med Genet Date: 2000-10-09
Authors: J T Williams; H Begleiter; B Porjesz; H J Edenberg; T Foroud; T Reich; A Goate; P Van Eerdewegh; L Almasy; J Blangero Journal: Am J Hum Genet Date: 1999-10 Impact factor: 11.025