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Study on GRIA2, GRIA3 and GRIA4 genes highlights a positive association between schizophrenia and GRIA3 in female patients

Authors

  • Chiara Magri,

    1. Division of Biology and Genetics, Department of Biomedical Sciences and Biotechnology, Brescia University School of Medicine, Viale Europa, Brescia, Italy
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  • Rita Gardella,

    1. Division of Biology and Genetics, Department of Biomedical Sciences and Biotechnology, Brescia University School of Medicine, Viale Europa, Brescia, Italy
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  • Paolo Valsecchi,

    1. Department of Mental Health, Brescia Spedali Civili, Piazza Spedali Civili, Brescia, Italy
    2. University Psychiatric Unit, Brescia University School of Medicine, Piazza Spedali Civili, Brescia, Italy
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  • Stefano Davide Barlati,

    1. Department of Mental Health, Brescia Spedali Civili, Piazza Spedali Civili, Brescia, Italy
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  • Luca Guizzetti,

    1. University Psychiatric Unit, Brescia University School of Medicine, Piazza Spedali Civili, Brescia, Italy
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  • Laura Imperadori,

    1. Division of Biology and Genetics, Department of Biomedical Sciences and Biotechnology, Brescia University School of Medicine, Viale Europa, Brescia, Italy
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  • Cristian Bonvicini,

    1. Genetics Unit, IRCCS ‘San Giovanni di Dio’ Associazione Fatebenefratelli per la Ricerca, Via Pilastroni, Brescia, Italy
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  • Gian Battista Tura,

    1. Psychiatric Rehabilitation Center IRCCS ‘San Giovanni di Dio’, Fatebenefratelli, Via Pilastroni, Brescia, Italy
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  • Massimo Gennarelli,

    1. Division of Biology and Genetics, Department of Biomedical Sciences and Biotechnology, Brescia University School of Medicine, Viale Europa, Brescia, Italy
    2. Genetics Unit, IRCCS ‘San Giovanni di Dio’ Associazione Fatebenefratelli per la Ricerca, Via Pilastroni, Brescia, Italy
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  • Emilio Sacchetti,

    1. Department of Mental Health, Brescia Spedali Civili, Piazza Spedali Civili, Brescia, Italy
    2. University Psychiatric Unit, Brescia University School of Medicine, Piazza Spedali Civili, Brescia, Italy
    3. Centre on Behavioural and Neurodegenerative Disorders, Brescia University and EULO, Brescia, Italy
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  • Prof. Sergio Barlati

    Corresponding author
    1. Division of Biology and Genetics, Department of Biomedical Sciences and Biotechnology, Brescia University School of Medicine, Viale Europa, Brescia, Italy
    2. Centre on Behavioural and Neurodegenerative Disorders, Brescia University and EULO, Brescia, Italy
    • Division of Biology and Genetics, Department of Biomedical Sciences and Biotechnology, Brescia University School of Medicine, Viale Europa 11, 25123 Brescia, Italy.
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  • Please cite this article as follows: Magri C, Gardella R, Valsecchi P, Barlati SD, Guizzetti L, Imperadori L, Bonvicini C, Tura GB, Gennarelli M, Sacchetti E, Barlati S. 2007. Study on GRIA2, GRIA3 and GRIA4 Genes Highlights a Positive Association Between Schizophrenia and GRIA3 in Female Patients. Am J Med Genet Part B 147B:745–753.

  • Emilio Sacchetti and Sergio Barlati contributed equally to this work.

Abstract

Impairment of glutamatergic neurotransmission is one of the major hypotheses proposed to explain the neurobiology of schizophrenia. Therefore, the genes involved in the glutamate neurotransmitter system could be considered potential candidate genes for schizophrenia susceptibility. A systematic study on alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor genes has been carried out and the results obtained from the analysis on GRIA2, GRIA3 and GRIA4 are reported. No evidence of association with schizophrenia was found for the GRIA2 and GRIA4 genes; strong evidence of association with schizophrenia was found for GRIA3. This X-linked gene showed a different behavior in the two genders; a positive association with schizophrenia was observed among females but not in males. Female carriers of rs1034428 A allele were found to have a 2.19-fold higher risk of developing schizophrenia compared to non-carriers and 3.28-fold higher risk for developing a non-paranoid phenotype. The analysis at the haplotype level showed that susceptibility to schizophrenia was associated with the specific haplotype rs989638–rs1034428–rs2227098 CAC (P = 0.0008). We conclude that, of the three AMPA genes analyzed here, only GRIA3 seems to be involved in the pathogenesis of schizophrenia, but only in females. © 2007 Wiley-Liss, Inc.

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