par Massat, Isabelle ;Souery, Daniel ;Del-Favero, Jurgen;Oruc, L;Noethen, M M;Blackwood, Douglas Hr;Thomson, Mike Andrew;Muir, W;Papadimitriou, George;Dikeos, Dimitris;Kaneva, Radka Petrova;Serretti, A;Lilli, R;Smeraldi, E;Jakovljevic, M;Folnegovic, V;Rietschel, Marcella;Milanova, V;Valente Soares, Filomena ;Van Broeckhoven, Christine;Mendlewicz, Julien
Référence Molecular psychiatry, 7, 2, page (201-207)
Publication Publié, 2002
Référence Molecular psychiatry, 7, 2, page (201-207)
Publication Publié, 2002
Article révisé par les pairs
Résumé : | 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. |