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

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.