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Association Between the G1001C Polymorphism in the GRIN1 Gene Promoter and Schizophrenia in the Iranian Population

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An Erratum to this article was published on 19 October 2008

Abstract

Schizophrenia is a complex genetic disorder to which genetic variation in the glutamatergic signaling pathways is believed to play a substantial role in the etiology of the disease. Association studies have implicated the N-methyl-d-aspartate receptor subunit gene, GRIN1, as a candidate gene for schizophrenia. In this report, we used a case control study to establish the possible association between the G1001C polymorphism in the GRIN1 gene promoter region and schizophrenia in an Iranian cohort of 200 unrelated patients and 200 controls. The allelic and genotypic frequencies of the polymorphism were determined using polymerase chain reaction restriction fragment length polymorphism. Data analysis using logistic regression and the Mantel–Haenszel chi-square test revealed a strong association between the G1001C polymorphism and schizophrenia (CG genotype: odds ratio (OR) = 2.12, 95% confidence interval (CI) 1.34–3.48, P = 0.001 and CC genotype: OR = 29.10, 95% CI 3.40–565.78, P < 0.001). Furthermore, the C allele is significantly associated with an increasing risk of schizophrenia.

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References

  • Allen, N. C., Bagade, S., McQueen, M. B., et al. (2008). Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: The SzGene database. Nature Genetics, 40(7), 827–834. doi:10.1038/ng.171.

    Article  PubMed  CAS  Google Scholar 

  • Begni, S., Moraschi, S., Bignotti, S., et al. (2003). Association between the G1001C polymorphism in the GRIN1 gene promoter region and schizophrenia. Biological Psychiatry, 53, 617–619. doi:10.1016/S0006-3223(02)01783-3.

    Article  PubMed  CAS  Google Scholar 

  • Bertram, L. (2008). Genetic research in schizophrenia: New tools and future perspectives. Schizophrenia Bulletin, 34, 806–812.

    Article  PubMed  Google Scholar 

  • Daw, N. W., Stein, P. S. G., Fox, K., et al. (1993). The role of NMDA receptors in information processing. Annual Review of Neuroscience 16, 207-222.

    Google Scholar 

  • Faraone, S. V., Matise, T., Svrakic, D., et al. (1998). Genome scan of European–American schizophrenia pedigrees: Results of the NIMH Genetics Initiative and Millennium Consortium. American Journal of Medical Genetics, 81, 290–295. doi:10.1002/(SICI)1096-8628(19980710)81:4<290::AID-AJMG3>3.0.CO;2-Y.

    Article  PubMed  CAS  Google Scholar 

  • Fujii, D. E., Wylie, A. M., & Nathan, J. H. (2004). Neurocognition and long-term prediction of quality of life in outpatients with severe and persistent mental illness. Schizophrenia Research, 69, 67–73. doi:10.1016/S0920-9964(03)00122-1.

    Article  PubMed  Google Scholar 

  • Georgi, A., Jamra, R. A., Klein, K. B., et al. (2007). Possible association between genetic variants at the GRIN1 gene and schizophrenia with lifetime history of depressive symptoms in a German sample. Psychiatric Genetics, 17(5), 308–310. doi:10.1097/YPG.0b013e3280c1e5fb.

    Article  PubMed  Google Scholar 

  • Goff, D. C., & Coyle, J. T. (2001). The emerging role of glutamate in the pathophysiology and treatment of schizophrenia. The American Journal of Psychiatry, 158, 1367–1377. doi:10.1176/appi.ajp.158.9.1367.

    Article  PubMed  CAS  Google Scholar 

  • Harrison, P. J., & Weinberger, D. R. (2005). Schizophrenia genes, gene expression, and neuropathology: On the matter of their convergence. Molecular Psychiatry, 10, 40–68. doi:10.1038/sj.mp.4001558.

    Article  PubMed  CAS  Google Scholar 

  • Hollmann, M., & Heinemann, S. (1994). Cloned glutamate receptors. Annual Review of Neuroscience, 17, 31–108. doi:10.1146/annurev.ne.17.030194.000335.

    Article  PubMed  CAS  Google Scholar 

  • Hung, C. C., Chen, H. Y., & Chen, C. H. (2002). Systematic mutation analysis of the human glutamate receptor, ionotropic, N-methyl-d-aspartate 1 gene (GRIN1) in schizophrenic patients. Psychiatric Genetics, 12, 225–230. doi:10.1097/00041444-200212000-00005.

    Article  PubMed  Google Scholar 

  • Jablensky, A. (2000). Epidemiology of schizophrenia: the global burden of disease and disability. European Archives of Psychiatry and Clinical Neuroscience, 250, 274–285. doi:10.1007/s004060070002.

    Article  PubMed  CAS  Google Scholar 

  • Javitt, D. C., & Zukin, S. R. (1991). Recent advances in the phencyclidine model of schizophrenia. The American Journal of Psychiatry, 148, 1301–1308.

    PubMed  CAS  Google Scholar 

  • Karasawa, J., Hashimoto, K., & Chali, S. H. (2008). d-Serine and a glycine transporter inhibitor improve MK-801-inducedcognitive deficits in a novel object recognition test in rats. Behavioural Brain Research, 186, 78–83. doi:10.1016/j.bbr.2007.07.033.

    Article  PubMed  CAS  Google Scholar 

  • Lane, H. Y., Chang, Y. C., Liu, Y. C., Chiu, C. C., & Tsai, G. E. (2005). Sarcosine or d-serine add-on treatment for acute exacerbation of schizophrenia: a randomized, double blind, placebo-controlled study. Archives of General Psychiatry, 62, 1196–1204. doi:10.1001/archpsyc.62.11.1196.

    Article  PubMed  CAS  Google Scholar 

  • Martucci, L., Wong, A. H., Trakalo, J., et al. (2003). N-methyl-d-aspartate receptor NR1 subunit gene (GRIN1) in schizophrenia: TDT and case-control analyses. American Journal of Medical Genetics, 119B, 24–27. doi:10.1002/ajmg.b.20014.

    Article  PubMed  Google Scholar 

  • McGuffin, P., Tandon, K., & Corsico, A. (2003). Linkage and association studies of schizophrenia. Current Psychiatry Reports, 5(2), 121–127. doi:10.1007/s11920-003-0028-y.

    Article  PubMed  Google Scholar 

  • Meador-Woodruff, J. H., & Healy, D. J. (2000). Glutamate receptor expression in schizophrenic brain. Brain Research Review, 31, 288–294.

    Article  CAS  Google Scholar 

  • Mohn, A. R., Gainetdinov, R. R., Caron, M. G., & Koller, B. H. (1999). Mice with reduced NMDA receptor expression display behaviors related to schizophrenia. Cell, 98, 427–436. doi:10.1016/S0092-8674(00)81972-8.

    Article  PubMed  CAS  Google Scholar 

  • Monyer, H., Sprengel, R., Schoepfer, R., et al. (1992). Heteromeric NMDA receptors: Molecular and functional distinction of subtypes. Science, 256, 1217–1221. doi:10.1126/science.256.5060.1217.

    Article  PubMed  CAS  Google Scholar 

  • Qin, S. H., Zhao, X., Pan, Y., et al. (2005). An association study of the N-methyl-d-aspartate receptor NR1 subunit gene (GRIN1) and NR2B subunit gene (GRIN2B) in schizophrenia with universal DNA microarray. European Journal of Human Genetics, 13, 807–814. doi:10.1038/sj.ejhg.5201418.

    Article  PubMed  CAS  Google Scholar 

  • Rice, S. R., Niu, N., Berman, D. B., Heston, L. L., & Sobell, J. L. (2001). Identification of single nucleotide polymorphisms (SNPs) and other sequence changes and estimation of nucleotide diversity in coding and flanking regions of the NMDAR1 receptor gene in schizophrenic patients. Molecular Psychiatry, 6, 274–284. doi:10.1038/sj.mp.4000838.

    Article  PubMed  CAS  Google Scholar 

  • Sakurai, K., Toru, M., Yamakawa-Kobayashi, K., & Arinami, T. (2000). Mutation analysis of the N-methyl-d-aspartate receptor NR1 subunit gene (GRIN1) in schizophrenia. Neuroscience Letters, 296, 168–170. doi:10.1016/S0304-3940(00)01599-8.

    Article  PubMed  CAS  Google Scholar 

  • Schork, N. J., Greenwood, T. A., & Braff, D. L. (2006). Statistical genetics concepts and approaches in schizophrenia and related neuropsychiatric research. Schizophrenia Bulletin, 33(1), 95–104. doi:10.1093/schbul/sbl045.

    Article  PubMed  Google Scholar 

  • Tani, A., Kikuta, R., Itoh, K., et al. (2002). Polymorphism analysis of the upstream region of the human N-methyl-d-aspartate receptor upstream region of the human N-methyl-d-aspartate receptor subunit NR1 gene (GRIN1): Implications for schizophrenia. Schizophrenia Research, 58, 83–86. doi:10.1016/S0920-9964(02)00161-5.

    Article  PubMed  Google Scholar 

  • VanDongen, A. M., & Van Dongen, H. M. (2004). Effects of mRNA untranslated regions on translational efficiency of NMDA receptor subunits. Neuro-Signals, 13, 194–206. doi:10.1159/000077526.

    Article  PubMed  CAS  Google Scholar 

  • Williams, N. M., Bowen, T., Spurlock, G., et al. (2002). Determination of the genomic structure and mutation screening in schizophrenic individuals for five subunits of the N-methyl-d-aspartate glutamate receptor. Molecular Psychiatry, 7, 508–514. doi:10.1038/sj.mp.4001030.

    Article  PubMed  CAS  Google Scholar 

  • Zhao, X., Li, H., Shi, Y., et al. (2006). Signification association between the genetic variations in the 5′ end of the N-methyl-d-aspartate receptor subunit gene GRIN1 and schizophrenia. Biological Psychiatry, 59, 747–753. doi:10.1016/j.biopsych.2005.10.023.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Shahid Chamran University, Ahvaz, Iran

    Hamid Galehdari

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  1. Hamid Galehdari
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Correspondence to Hamid Galehdari.

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An erratum to this article can be found at http://dx.doi.org/10.1007/s12031-008-9152-9

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Galehdari, H. Association Between the G1001C Polymorphism in the GRIN1 Gene Promoter and Schizophrenia in the Iranian Population. J Mol Neurosci 38, 178–181 (2009). https://doi.org/10.1007/s12031-008-9148-5

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  • DOI: https://doi.org/10.1007/s12031-008-9148-5

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