Excess of allelel for a3 subunit GABA receptor gene (GABRA3) in bipolar patients: a multicentric
association study
Auteur(s) / Author(s)
MASSAT I. (1) ; SOUERY D. (1) ; DEL-FAVERO J. (2) ; ORUC L. (3) ; NOETHEN M. M. (4) ; BLACKWOOD D. (5) ;
THOMSON M. (5) ; MUIR W. (5) ; PAPADIMITRIOU G. N. (6) ; DIKEOS D. G. (6) ; KANEVA R. (7) ; SERRETTI A. (8) ;
LILLI R. (8) ; SMERALDI E. (8) ; JAKOVLJEVIC M. (9) ; FOLNEGOVIC V. (9) ; RIETSCHEL M. (10) ; MILANOVA V.
(11) ; VALENTE F. (12) ; VAN BROECKHOVEN C. (2) ; MENDLEWICZ J. (1) ;
Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)
(1)
Department of Psychiatry, University Clinics of Brussels, Erasme Hospital, Free University of Brussels,
BELGIQUE
(2) Department of Molecular Genetics, Flanders Interuniveristy Institute for Biotechnology (VIB), University
of
Antwerp
(UIA),
Antwerpen,
BELGIQUE
(3)
Psychiatry
Clinic,
University
of
Sarajevo,
Sarajevo,
BOSNIE-HERZEGOVINE
(4)
Institute
of
Human
Genetics,
University
of
Bonn,
ALLEMAGNE
(5) Department of Psychiatry and the Department of Medical Science, University of Edinburgh, ROYAUMEUNI
(6) Athens University Medical School, Department of Psychiatry and University Mental Health Research
Institute,
Athens,
GRECE
(7) Laboratory of Molecular Pathology, University Hospital of Obstetrics, Medical University, Sofia,
BULGARIE
(8) Instituto Scientifico H San Raffaele, Department of Neuroscience, University of Milano School of
Medicine,
Milan,
ITALIE
(9) Department of Psychiatry, University Hospital REBRO', University of Zagreb, Zagreb, CROATIE
(10)
Department
of
Psychiatry,
University
of
Bonn,
Bonn,
ALLEMAGNE
(11) First Psychiatric Clinic, Department of Psychiatry, Alexander University Hospital, Sofia, BULGARIE
(12) Department of Statistics, School of Public Health, Free University of Brussels, BELGIQUE
Résumé / 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 a3 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.
Revue / Journal Title
Molecular psychiatry ISSN 1359-4184
Source / Source
2002, vol. 7, no2, pp. 201-207 (50 ref.)
Langue / Language
Anglais
Editeur / Publisher
Nature Publishing Group, Basingstoke, ROYAUME-UNI (1996) (Revue)