• Alcohol Dependence;
  • Dissocial Personality Disorder;
  • GABAA Receptor Genes;
  • Association;
  • Genetics

Quantitative trait analyses in mice suggest a vulnerability locus for physiological alcohol withdrawal severity on a chromosomal segment that harbors the genes encoding the α1, α6, β2, and γ2 subunits of the γ2-aminobutyric acid type-A receptor (GABR). We tested whether genetic variation at the human GABAAα6, β2, and γ2 gene cluster on chromosome 5q33 confers vulnerability to alcohol dependence. The genotypes of three nucleotide substitution polymorphisms of the GABRA6, GABRB2, and GABRG2 genes were assessed in 349 German alcohol-dependent subjects and in 182 ethnically matched controls. To eliminate some of the genetic variance, three more homogeneous subgroups of alcoholics were formed by: (1) a history of alcohol withdrawal seizure or delirium (n= 106); (2) a history of parental alcoholism (n= 120); and (3) a comorbidity of dissocial personality disorder (n= 57). We found no evidence that any of the investigated allelic variants confers vulnerability to either alcohol dependence or severe physiological alcohol withdrawal symptoms or familial alcoholism (p > 0.05). The frequency of the T allele of the GABRA6 polymorphism was significantly increased in dissocial alcoholics [f(T) = 0.799] compared with the controls [f(T) = 0.658; p = 0.002; OR(T+) = 7.26]. Taking into account the high a priori risk of false-positive association findings due to multiple testing, further replication studies are necessary to examine the tentative phenotype-genotype relationship of GABRA6 gene variants and dissocial alcoholism.