Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Research Article
  • Published:

Association between the ionotropic glutamate receptor kainate 3 (GRIK3) ser310ala polymorphism and schizophrenia

Molecular Psychiatry volume 7, pages 416–418 (2002)Cite this article

Abstract

Schizophrenia is a severe psychiatric illness characterised by disturbance of thought, hallucination and delusions.1 Several studies have suggested that dysfunctions in the glutamatergic transmission are linked to the pathogenesis of schizophrenia, and in particular an excessive activation of glutamate receptors seems to be related to the disruption of neuronal ionic gradients leading to excitotoxicity.2–7 Numerous findings suggested that the kainate ionotropic glutamate receptors are primarily involved in this mechanism. Recently it has been demonstrated that the GRIK3 gene encoding for the ionotropic glutamate receptor kainate 3 contains a functional polymorphism (T928G) leading to the substitution of a serine with an alanine in position 310 of the protein sequence.8–11 We performed an association study between the ser310ala GRIK3polymorphism and schizophrenia in a sample of 99 schizophrenic patients and 116 controls. We found a significant difference in the genotype distribution and in particular considering the ala allele as dominant (P = 0.0105, odds ratio (OR) 2.031, 95% confidence interval (CI) 1.177–3.504). This finding suggests a potential role for GRIK3 for susceptibility to schizophrenia.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Kendler KS The genetics of schizophrenia: an overview. In: Tsuang MT, Simpson JC (eds) Handbook of Schizophrenia, Volume 3, Nosology, Epidemiology and Genetics of Schizophrenia Elsevier: Amsterdam 1988 437 462

    Google Scholar 

  2. Coyle JT The glutamatergic dysfunction hypothesis for schizophrenia Harv Rev Psychiatry 1996 3 241 253

    Article  CAS  Google Scholar 

  3. Dingledine R Borges K Bowie D Traynelis SF The glutamate receptor ion channels Pharmacol Rev 1999 51 7 61

    CAS  PubMed  Google Scholar 

  4. Heckers S Rauch SL Goff D Savage CR Schacter DL Fischman AJ et alImpaired recruitment of the hippocampus during conscious recollection in schizophrenia Nat Neurosci 1998 1 318 323

    Article  CAS  Google Scholar 

  5. Benes FM Sorensen I Vincent SL Bird ED Sathi M Increased density of glutamate-immunoreactive vertical processes in superficial laminae in cingulate cortex of schizophrenic brain Cereb Cortex 1992 2 503 512

    Article  CAS  Google Scholar 

  6. Benes FM Emerging principles of altered neural circuitry in schizophrenia Brain Res Brain Res Rev 2000 31 251 269

    Article  CAS  Google Scholar 

  7. Lipton SA Rosenberg PA Excitatory amino acids as a final common pathway for neurologic disorders N Engl J Med 1994 330 613 622

    Article  CAS  Google Scholar 

  8. Schiffer HH Swanson GT Masliah E Heinemann F Unequal expression of allelic kainate receptor GluR7 mRNAs in human brains J Neurosci 2000 20 9025 9033

    Article  CAS  Google Scholar 

  9. Meador-Woodruff JH Davis KL Haroutunian V Abnormal kainate receptor expression in prefrontal cortex in schizophrenia Neuropsychopharmacology 2001 24 545 552

    Article  CAS  Google Scholar 

  10. Strutz N Villmann C Thalhammer A Kizelsztein P Eisenstein M Teichberg VI et alIdentification of domains and amino acids involved in GluR7 ion channel function J Neurosci 2001 21 401 411

    Article  CAS  Google Scholar 

  11. Nutt SL Hoo KH Rampersad V Deverill RM Elliott CE Fletcher EJ et alMolecular characterization of the human EAA5 (GluR7) receptor: a high-affinity kainate receptor with novel potential RNA editing sites Receptors Channels 1994 2 315 326

    CAS  PubMed  Google Scholar 

  12. Guruprasad K Reddy BV Pandit MW Correlation between stability of a protein and its dipeptide composition: a novel approach for predicting in vivo stability of a protein from its primary sequence Protein Eng 1990 4 155 161

    Article  CAS  Google Scholar 

  13. Krupp JJ Vissel B Heinemann SF Westbrook GL N-terminal domains in the NR2 subunit control desensitization of NMDA receptors Neuron 1998 20 317 327

    Article  CAS  Google Scholar 

  14. Armstrong N Sun Y Chen GQ Gouaux E Structure of a glutamate-receptor ligand-binding core in complex with kainate Nature 1998 395 913 917

    Article  CAS  Google Scholar 

  15. Thalhammer A Morth T Strutz N Hollmann M A desensitization-inhibiting mutation in the glutamate binding site of rat alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor subunits is dominant in heteromultimeric complexes Neurosci Lett 1999 277 161 164

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This research was supported by a grant from the Italian Ministry of Health and the Cariplo Foundation.

Author information

Authors and Affiliations

  1. Genetics Unit, IRCCS ‘S Giovanni di Dio’, Fatebenefratelli, Brescia, 25123, Italy

    S Begni, S Moraschi & M Gennarelli

  2. Center of Neuropharmacology, Institute of Pharmacological Sciences, University of Milan, Milan, 20133, Italy

    M Popoli

  3. Psychiatric Rehabilitation Unit, IRCCS ‘S Giovanni di Dio’, Fatebenefratelli, Brescia, 25123, Italy

    S Bignotti & G B Tura

Authors
  1. S Begni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M Popoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S Moraschi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S Bignotti
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G B Tura
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M Gennarelli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M Gennarelli.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Begni, S., Popoli, M., Moraschi, S. et al. Association between the ionotropic glutamate receptor kainate 3 (GRIK3) ser310ala polymorphism and schizophrenia. Mol Psychiatry 7, 416–418 (2002). https://doi.org/10.1038/sj.mp.4000987

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.mp.4000987

Keywords

This article is cited by

Search

Advanced search

Quick links