Excess of allele1 for α3 subunit GABA receptor gene (GABRA3) in bipolar patients: A multicentric association study

I. Massat, D. Souery, J. Del-Favero, L. Oruc, M. M. Noethen, D. Blackwood, M. Thomson, W. Muir, G. N. Papadimitriou, D. G. Dikeos, R. Kaneva, A. Serretti, R. Lilli, E. Smeraldi, M. Jakovljevic, V. Folnegovic, M. Rietschel, V. Milanova, F. Valente, C. Van BroeckhovenJ. Mendlewicz

Research output: Contribution to journalArticle

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 α3 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.

Original languageEnglish
Pages (from-to)201-207
Number of pages7
JournalMolecular Psychiatry
Volume7
Issue number2
DOIs
Publication statusPublished - 2002

Keywords

  • Association study
  • Bipolar disorder
  • Candidate gene
  • Chromosome X
  • GABRA3

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health

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    Massat, I., Souery, D., Del-Favero, J., Oruc, L., Noethen, M. M., Blackwood, D., Thomson, M., Muir, W., Papadimitriou, G. N., Dikeos, D. G., Kaneva, R., Serretti, A., Lilli, R., Smeraldi, E., Jakovljevic, M., Folnegovic, V., Rietschel, M., Milanova, V., Valente, F., ... Mendlewicz, J. (2002). Excess of allele1 for α3 subunit GABA receptor gene (GABRA3) in bipolar patients: A multicentric association study. Molecular Psychiatry, 7(2), 201-207. https://doi.org/10.1038/sj/mp/4000953