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GRM7 polymorphisms and risk of schizophrenia in Iranian population

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Abstract

The role of metabotropic glutamate receptors in the pathogenesis of schizophrenia or response to antipsychotic treatment has been proposed previously. The aim of the current study was to investigate the associations between two intronic variants within GRM7 gene (rs6782011 and rs779867) and schizophrenia in Iranian population. These two single nucleotide polymorphisms (SNPs) were genotyped in 273 schizophrenic patients and 300 age and sex-matched normal controls. The frequency of A allele of the rs779867 was significantly lower in the schizophrenic patients compared with healthy subjects (OR (95% CI) = 0.71 (0.56–0.89), adjusted P value = 0.008). This SNP was associated with schizophrenia in co-dominant and dominant models (adjusted P values of 0.03 and 0.02 respectively). However, there was no difference in allele and genotype frequencies of the rs6782011 SNP between cases and controls. Consequently, the results of current study further highlight the participation of GRM7 in the pathogenesis of schizophrenia.

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References

  • Association, D.-A. P. 2013. Diagnostic and statistical manual of mental disorders. Arlington: American Psychiatric Publishing

  • Bertram MJ, Pereira-Smith OM (2001) Conservation of the MORF4related gene family: identification of a new chromo domain subfamily and novel protein motif. Gene 266:111–121

    Article  CAS  PubMed  Google Scholar 

  • Bertram M, Berube N, Hang-Swanson X, Ran Q, Leung J, Bryce S, Spurgers K, Bick R, Baldini A, Ning Y (1999) Identification of a gene that reverses the immortal phenotype of a subset of cells and is a member of a novel family of transcription factor-like genes. Mol Cell Biol 19:1479–1485

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cohen A, Patel V, Thara R, Gureje O (2008) Questioning an axiom: better prognosis for schizophrenia in the developing world? Schizophr Bull 34:229–244

    Article  PubMed  Google Scholar 

  • Drahl C (2008) Rethinking schizophrenia. Chem Eng News 86:38–40

    Google Scholar 

  • Fell MJ, Svensson KA, Johnson BG, Schoepp DD (2008) Evidence for the role of metabotropic glutamate (mGlu)2 not mGlu3 receptors in the preclinical antipsychotic pharmacology of the mGlu2/3 receptor agonist (−)-(1R,4S,5S,6S)-4-amino-2-sulfonylbicyclo[3.1.0]hexane-4,6-dicarboxylic acid (LY404039). J Pharmacol Exp Ther 326:209–217

    Article  CAS  PubMed  Google Scholar 

  • Ganda C, Schwab SG, Amir N, Heriani H, Irmansyah I, Kusumawardhani A, Nasrun M, Widyawati I, Maier W, Wildenauer DB (2009) A family-based association study of DNA sequence variants in GRM7 with schizophrenia in an Indonesian population. Int J Neuropsychopharmacol 12:1283–1289

    Article  CAS  PubMed  Google Scholar 

  • Gray L, van den Buuse M, Scarr E, Dean B, Hannan AJ (2009) Clozapine reverses schizophrenia-related behaviours in the metabotropic glutamate receptor 5 knockout mouse: association with N-methyl-D-aspartic acid receptor up-regulation. Int J Neuropsychopharmacol 12:45–60

    Article  CAS  PubMed  Google Scholar 

  • Halene TB, Peter CJ, Akbarian S (2014) Epigenetic dysregulation in the schizophrenic brain. Curr Behav Neurosci Rep 1:86–93

    Article  Google Scholar 

  • Irmansyah, Schwab SG, Heriani, Handoko HY, Kusumawardhani A, Widyawati I, Amir N, Nasrun MWS, Holmans P, Knapp M, Wildenauer DB (2008) Genome-wide scan in 124 Indonesian sib-pair families with schizophrenia reveals genome-wide significant linkage to a locus on chromosome 3p26-21. Am J Med Genet B Neuropsychiatr Genet 147B:1245–1252

    Article  Google Scholar 

  • Jalan-Sakrikar N, Field JR, Klar R, Mattmann ME, Gregory KJ, Zamorano R, Engers DW, Bollinger SR, Weaver CD, Days EL, Lewis LM, Utley TJ, Hurtado M, Rigault D, Acher F, Walker AG, Melancon BJ, Wood MR, Lindsley CW, Conn PJ, Xiang ZX, Hopkins CR, Niswender CM (2014) Identification of positive allosteric modulators VU0155094 (ML397) and VU0422288 (ML396) reveals new insights into the biology of metabotropic glutamate receptor 7. ACS Chem Neurosci 5:1221–1237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li W, Ju K, Li Z, He K, Chen J, Wang Q, Yang B, An L, Feng G, Sun W, Zhou J, Zhang S, Song P, Khan RAW, Ji W, Shi Y (2016) Significant association of GRM7 and GRM8 genes with schizophrenia and major depressive disorder in the Han Chinese population. Eur Neuropsychopharmacol 26:136–146

    Article  CAS  PubMed  Google Scholar 

  • Lisman JE, Coyle JT, Green RW, Javitt DC, Benes FM, Heckers S, Grace AA (2008) Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia. Trends Neurosci 31:234–242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu, Y., Quan, C., Chen, H., Bo, X. & Zhang, C. 2016. 3DSNP: a database for linking human noncoding SNPs to their three-dimensional interacting genes. Nucleic acids research , gkw1022

  • Marsman A, van den Heuvel MP, Klomp DW, Kahn RS, Luijten PR, Hulshoff Pol HE (2011) Glutamate in schizophrenia: a focused review and meta-analysis of 1H-MRS studies. Schizophr Bull 39:120–129

    Article  PubMed  PubMed Central  Google Scholar 

  • Moghaddam B, Adams BW (1998) Reversal of phencyclidine effects by a group II metabotropic glutamate receptor agonist in rats. Science 281:1349–1352

    Article  CAS  PubMed  Google Scholar 

  • Niu W, Huang X, Yu T, Chen S, Li X, Wu X, Cao Y, Zhang R, Bi Y, Yang F (2015) Association study of GRM7 polymorphisms and schizophrenia in the Chinese Han population. Neurosci Lett 604:109–112

    Article  CAS  PubMed  Google Scholar 

  • Noroozi R, Taheri M, Movafagh A, Mirfakhraie R, Solgi G, Sayad A, Mazdeh M, Darvish H (2016) Glutamate receptor, metabotropic 7 (GRM7) gene variations and susceptibility to autism: a case-control study. Autism Res 9:1161–1168

    Article  PubMed  Google Scholar 

  • Nothen MM, Nieratschker V, Cichon S, Rietschel M (2010) New findings in the genetics of major psychoses. Dialogues Clin Neurosci 12:85–93

    PubMed  PubMed Central  Google Scholar 

  • Ohtsuki T, Koga M, Ishiguro H, Horiuchi Y, Arai M, Niizato K, Itokawa M, Inada T, Iwata N, Iritani S, Ozaki N, Kunugi H, Ujike H, Watanabe Y, Someya T, Arinami T (2008) A polymorphism of the metabotropic glutamate receptor mGluR7 (GRM7) gene is associated with schizophrenia. Schizophr Res 101:9–16

    Article  PubMed  Google Scholar 

  • Ossowska K, Pietraszek M, Wardas J, Nowak G, Zajaczkowski W, Wolfarth S, Pilc A (2000) The role of glutamate receptors in antipsychotic drug action. Amino Acids 19:87–94

    Article  CAS  PubMed  Google Scholar 

  • Patil ST, Zhang L, Martenyi F, Lowe SL, Jackson KA, Andreev BV, Avedisova AS, Bardenstein LM, Gurovich IY, Morozova MA, Mosolov SN, Neznanov NG, Reznik AM, Smulevich AB, Tochilov VA, Johnson BG, Monn JA, Schoepp DD (2007) Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized phase 2 clinical trial. Nat Med 13:1102–1107

    Article  CAS  PubMed  Google Scholar 

  • Rahimi S, Sayad A, Moslemi E, Ghafouri-FARD S, Taheri M (2017) Blood assessment of the expression levels of matrix metalloproteinase 9 (MMP9) and its natural inhibitor, TIMP1 genes in Iranian schizophrenic patients. Metab Brain Dis 32:1537–1542

    Article  CAS  PubMed  Google Scholar 

  • Ward LD, Kellis M (2011) HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants. Nucleic Acids Res 40:D930–D934

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang Y, Pan C (2013) Role of metabotropic glutamate receptor 7 in autism spectrum disorders: a pilot study. Life Sci 92:149–153

    Article  CAS  PubMed  Google Scholar 

  • Yoo J, Lee Y, Kim Y, Rha SY, Kim Y (2008) SNPAnalyzer 2.0: a web-based integrated workbench for linkage disequilibrium analysis and association analysis. BMC Bioinformatics 9:290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The current study was supported by a grant from Shahid Beheshti University of Medical Sciences.

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Correspondence to Soudeh Ghafouri-Fard or Mohammad Taheri.

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Azari, I., Moghadam, R.H., Fallah, H. et al. GRM7 polymorphisms and risk of schizophrenia in Iranian population. Metab Brain Dis 34, 847–852 (2019). https://doi.org/10.1007/s11011-018-0380-6

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