Association analysis of exonic variants of the gene encoding the GABAB receptor and alcohol dependence

Psychiatr Genet. 1999 Jun;9(2):69-73. doi: 10.1097/00041444-199906000-00004.

Abstract

The present association study tested whether genetic variation of the GABAB receptor (GABABR1) gene confers vulnerability to alcohol dependence. The genotypes of three DNA sequence variants in exons 1a1, 7 and 11 of the GABABR1 gene were assessed in 234 German controls and 350 German alcohol-dependent subjects, including three more homogeneous subgroups of alcoholics, marked by (1) history of parental alcoholism (n = 121); (2) history of alcohol withdrawal seizure or delirium (n = 108); and (3) comorbidity of dissocial personality disorder (n = 60). The allele frequencies of none of the investigated GABABR1 variants differed significantly between the controls and the groups of alcoholics when a correction for multiple testing was taken into account (P > 0.004). However, trends (P < 0.10) towards an excess of the Ser489 allele of the exon 7 polymorphism were found in the subgroups of alcoholics, and of the common allele of the exon 11 polymorphism in the entire sample of alcoholics (P = 0.032), alcoholics with parental alcoholism (P = 0.084) and the dissocial alcoholics (P = 0.037). Our findings suggest that the investigated GABABR1 variants do not contribute a substantial effect (RR > 3) to the genetic variance of alcohol dependence. Nevertheless, the hints towards potential allelic associations of the exon 7 and 11 polymorphisms with dissocial alcoholism emphasize further studies to test more defined phenotype-genotype relationships.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alcoholism / genetics*
  • DNA / blood
  • DNA / genetics
  • Exons
  • Female
  • Genetic Predisposition to Disease / genetics
  • Genetic Variation*
  • Genotype
  • Humans
  • Male
  • Polymorphism, Restriction Fragment Length
  • Receptors, GABA-B / genetics*
  • Reference Values

Substances

  • Receptors, GABA-B
  • DNA