title: Excess of allele1 for alpha3 subunit GABA receptor gene (GABRA3) in bipolar patients: a multicentric association study.
abstract: The available data from preclinical and pharmacological studies on the role of gamma amino butyric acid (GABA) support the hypothesis that a dysfunction in brain GABAergic system activity contributes to the vulnerability to bipolar affective disorders (BPAD). Moreover, the localization of the alpha3 subunit GABA receptor GABRA3 gene on the Xq28, a region of interest in certain forms of bipolar illness, suggests that GABRA3 may be a candidate gene in BPAD. In the present study, we tested the genetic contribution of the GABRA3 dinucleotide polymorphism in a European multicentric case-control sample, matched for sex and ethnogeographical origin. Allele and genotype (in females) frequencies were compared in 185 BPAD patients and 370 controls. A significant increase of genotype 1-1 was observed in BPAD females compared to controls (P=0.0004). Furthermore, when considering recessivity of allele 1 (females with genotype 1-1 and males carrying allele 1), results were even more significant (P= 0.00002). Our findings suggest that the GABRA3 polymorphism may confer susceptibility to or may be in linkage disequilibrium with another gene involved in the genetic etiology of BPAD.
authors.affiliation: Department of Psychiatry, University Clinics of Brussels, Erasme Hospital, Free University of Brussels, Belgium. imassat@ulb.ac.be
authors.forename: I
authors.initials: I
authors.lastname: Massat
authors.forename: D
authors.initials: D
authors.lastname: Souery
authors.forename: J
authors.initials: J
authors.lastname: Del-Favero
authors.forename: L
authors.initials: L
authors.lastname: Oruc
authors.forename: M M
authors.initials: MM
authors.lastname: Noethen
authors.forename: D
authors.initials: D
authors.lastname: Blackwood
authors.forename: M
authors.initials: M
authors.lastname: Thomson
authors.forename: W
authors.initials: W
authors.lastname: Muir
authors.forename: G N
authors.initials: GN
authors.lastname: Papadimitriou
authors.forename: D G
authors.initials: DG
authors.lastname: Dikeos
authors.forename: R
authors.initials: R
authors.lastname: Kaneva
authors.forename: A
authors.initials: A
authors.lastname: Serretti
authors.forename: R
authors.initials: R
authors.lastname: Lilli
authors.forename: E
authors.initials: E
authors.lastname: Smeraldi
authors.forename: M
authors.initials: M
authors.lastname: Jakovljevic
authors.forename: V
authors.initials: V
authors.lastname: Folnegovic
authors.forename: M
authors.initials: M
authors.lastname: Rietschel
authors.forename: V
authors.initials: V
authors.lastname: Milanova
authors.forename: F
authors.initials: F
authors.lastname: Valente
authors.forename: C
authors.initials: C
authors.lastname: Van Broeckhoven
authors.forename: J
authors.initials: J
authors.lastname: Mendlewicz
mesh_terms: D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics*; D016022:Case-Control Studies; D005060:Europe; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D011110:Polymorphism, Genetic; D018079:Receptors, GABA / Q000235:genetics*; D014960:X Chromosome
chemical_list: D018079:Receptors, GABA