This study was supported by the Peacock Foundation, the Psychiatry Research Trust, the Deutsche Forschungsgemeinschaft (He 916/7-2), and an Alexander von Humboldt Stiftung Fellowship (to J.S.).
Association Analysis of Sequence Variants of the GABAAα6, β2, and γ2 Gene Cluster and Alcohol Dependence
Article first published online: 30 MAY 2006
Alcoholism: Clinical and Experimental Research
Volume 23, Issue 3, pages 427–431, March 1999
How to Cite
Sander, T., Ball, D., Murray, R., Patel, J., Samochowiec, J., Winterer, G., Rommelspacher, H., Schmidt, L. G. and Loh, E.-W. (1999), Association Analysis of Sequence Variants of the GABAAα6, β2, and γ2 Gene Cluster and Alcohol Dependence. Alcoholism: Clinical and Experimental Research, 23: 427–431. doi: 10.1111/j.1530-0277.1999.tb04133.x
- Issue published online: 30 MAY 2006
- Article first published online: 30 MAY 2006
- Received for publication August 20, 1998: accepted December 23, 1998.
- Alcohol Dependence;
- Dissocial Personality Disorder;
- GABAA Receptor Genes;
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.