title: Association of GABAA receptor α2 subunit gene (GABRA2) with alcohol dependence-related aggressive behavior.
abstract: Alcohol dependence is a common chronic disorder precipitated by the complex interaction between biological, genetic and environmental risk factors. Recent studies have demonstrated that polymorphisms of the gene encoding the GABAA receptor α2 subunit (GABRA2) are associated with alcohol dependence in different populations of European ancestry. As aggression often occurs in the context of alcohol dependence, the aim of this study was to examine the allelic and haplotypic association of GABRA2 gene with alcohol dependence and related aggressive behavior in subjects of Eastern European (Croatian) origin. Genotyping of the 3 single nucleotide polymorphisms (SNPs) across the GABRA2 gene (rs567926, rs279858 and rs9291283) was performed in patients with alcohol dependence (N=654) and healthy control subjects (N=574). Alcohol-dependent participants were additionally subdivided according to the presence/absence of aggressive behavior and type of alcohol dependence according to the Cloninger's classification. The association of rs279858 with alcohol dependence yielded nominal significance level. Haplotype analysis revealed a high degree of linkage disequilibrium (LD) for rs567926 and rs279858, but not for rs9291283 polymorphism in the GABRA2 gene. In patients with alcohol dependence, the A-C (rs567926 and rs279858) haplotype carriers were more likely to demonstrate aggressive behavior. The same haplotype (present only in 1.6% of all subjects) was significantly more often present in patients with a combination of early onset alcohol abuse and aggression, corresponding to the Cloninger's type II alcoholism subgroup. These findings support the involvement of GABRA2 gene in alcohol dependence-related aggressive behavior.
authors.affiliation: Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia. Electronic address: dsvob@irb.hr.
authors.forename: Dubravka Svob
authors.initials: DS
authors.lastname: Strac
authors.affiliation: Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia.
authors.forename: Gordana Nedic
authors.initials: GN
authors.lastname: Erjavec
authors.affiliation: Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia.
authors.forename: Matea Nikolac
authors.initials: MN
authors.lastname: Perkovic
authors.affiliation: Center for Alcoholism and Other Addictions, Psychiatric Hospital Vrapce, Zagreb, Croatia.
authors.forename: Korona Nenadic
authors.initials: KN
authors.lastname: Sviglin
authors.affiliation: Department for Functional Genomics, Center for Translational and Clinical Research, School of Medicine, University of Zagreb, University Hospital Center Zagreb, Zagreb, Croatia.
authors.forename: Fran
authors.initials: F
authors.lastname: Borovecki
authors.affiliation: Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia. Electronic address: npivac@irb.hr.
authors.forename: Nela
authors.initials: N
authors.lastname: Pivac
mesh_terms: D000328:Adult; D000374:Aggression; D000437:Alcoholism / Q000235:genetics* / Q000503:physiopathology*; D000704:Analysis of Variance; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011963:Receptors, GABA-A / Q000235:genetics*; D044465:White People
chemical_list: C484841:GABRA2 protein, human; D011963:Receptors, GABA-A
keywords: Aggression; Alcohol dependence; Cloninger's classification; GABRA2; Haplotype; Polymorphism