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Association of schizophrenia with variants of genes that encode transcription factors

  • Genomics. Transcriptomics
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Abstract

Transcription factors c-Fos, c-Jun, and Ier5 are important regulators of neuronal plasticity and immune response. In the present work, several single nucleotide polymorphisms of the genes that encode c-Fos-,c-Jun-, and Ier5 (FOS, JUN, and IER5, respectively) were investigated for potential association with schizophrenia. DNA samples obtained from patients with schizophrenia and healthy individuals were genotyped by polymerase chain reaction with allele-specific primers. It was shown that FOS rs1063169, FOS rs7101, JUN rs11688, and IER5 rs6425663 polymorphisms were associated with schizophrenia. In particular, the risk of schizophrenia was decreased in carriers of the minor alleles FOS rs1063169*T, JUN rs11688*A, and IER5 rs6425663*T, but increased in carriers of the FOS rs7101*T minor variant, especially in homozygotes.

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References

  1. van Os J., Rutten B.P., Poulton R. 2008. Gene–environment interactions in schizophrenia: Review of epidemiological findings and future directions. Schizophr. Bull. 34, 1066–1082.

    Article  PubMed Central  PubMed  Google Scholar 

  2. Uranova N.A. 1996. Brain synaptic plasticity in schizophrenia. Vestn. Ross. Akad. Med. Nauk. 4, 23–28.

    PubMed  Google Scholar 

  3. Stephan K.E., Baldeweg T., Friston K.J. 2006. Synaptic plasticity and dysconnection in schizophrenia. Biol. Psychiatry. 59, 929–939.

    Article  CAS  PubMed  Google Scholar 

  4. Yin D.M., Chen Y.J., Sathyamurthy A., Xiong W.C., Mei L. 2012. Synaptic dysfunction in schizophrenia. Adv. Exp. Med. Biol. 970, 493–516.

    Article  CAS  PubMed  Google Scholar 

  5. Klyushnik T.P., Shcherbakova I.V. 2005. Immune system and schizophrenia: Clinical-biological relationship. Psikhiatriya. 6, 48–61.

    Google Scholar 

  6. Müller N., Schwarz M.J. 2010. Immune system and schizophrenia. Curr. Immunol. Rev. 6, 213–220.

    Article  PubMed Central  PubMed  Google Scholar 

  7. Boyajyan A., Zakharyan R., Khoyetsyan A. 2012. Molecular and genetic indicators of aberrant immunity and apoptosis in schizophrenia. In: Schizophrenia Research: Recent Advances, Ed. Sumiyoshi T., Hauppauge, NY: Nova Science Publ., pp. 183–240.

    Google Scholar 

  8. Kolyaskina G.I., Sekirina T.P. 1990. Immunology of schizophrenia. Current problems and perspectives. Med. Referat. Zh. Psichiatriya. 3, 6–9.

    Google Scholar 

  9. Klyushnik T.P., Liderman R.R. 2010. Autoimmune mechanisms in the genesis of alterations of the nervous system development. Vestn. Ross. Akad. Med. Nauk. 7, 32–34.

    Google Scholar 

  10. Zakharyan R., Boyajyan A. 2014. Inflammatory cytokine network in schizophrenia. World J. Biol. Psychiatry. 15, 174–187.

    Article  PubMed  Google Scholar 

  11. Fleischmann A., Hvalby O., Jensen V., et al. 2003. Impaired long-term memory and NR2A-type NMDA receptor-dependent synaptic plasticity in mice lacking c-Fos in the CNS. J. Neurosci. 23, 9116–9122.

    CAS  PubMed  Google Scholar 

  12. Kristiansen L.V., Huerta I., Beneyto M., MeadorWoodruff J.H. 2007. NMDA receptors and schizophrenia. Curr. Opin. Pharmacol. 7, 48–55.

    Article  CAS  PubMed  Google Scholar 

  13. Vanhoutte P., Barnier J.V., Guibert B., Pagès C., Besson M.J., Hipskind R.A., Caboche J. 1999. Glutamate induces phosphorylation of Elk-1 and CREB, along with c-fos activation, via an extracellular signal-regulated kinase-dependent pathway in brain slices. Mol. Cell. Biol. 19, 136–146.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Bartzokis G. 2002. Schizophrenia: Breakdown in the well-regulated lifelong process of brain development and maturation. Neuropsychopharmacology. 27, 672–683.

    Article  PubMed  Google Scholar 

  15. Fatemi S.H., Folsom T.D. 2009. The neurodevelopmental hypothesis of schizophrenia, revisited. Schizophr. Bull. 35, 528–548.

    Article  PubMed Central  PubMed  Google Scholar 

  16. Torkamani A., De B., Thomas E.A. 2010. Coexpression network analysis of neural tissue reveals perturbations in developmental processes in schizophrenia. Genome Res. 20, 403–412.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Zhao A., Li M. 2012. Neuroanatomical substrates of the disruptive effect of olanzapine on rat maternal behavior as revealed by c-Fos immunoreactivity. Pharmacol. Biochem. Behav. 103, 174–180.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Zamberletti E., Viganò D., Guidali C., Rubino T., Parolaro D. 2012. Long-lasting recovery of psychoticlike symptoms in isolation-reared rats after chronic but not acute treatment with the cannabinoid antagonist AM251. Int. J. Neuropsychopharmacol. 15, 267–280.

    Article  CAS  PubMed  Google Scholar 

  19. Brady A.M., Saul R.D., Wiest M.K. 2010. Selective deficits in spatial working memory in the neonatal ventral hippocampal lesion rat model of schizophrenia. Neuropharmacology. 59, 605–611.

    Article  CAS  PubMed  Google Scholar 

  20. Glover J.N., Harrison S.C. 1995. Crystal structure of the heterodimericb ZIP transcription factor c-Fos–cJun bound to DNA. Nature. 373, 257–261.

    Article  CAS  PubMed  Google Scholar 

  21. Alberini C.M. 2009. Transcription factors in long-term memory and synaptic plasticity. Physiol. Rev. 89, 121–145.

    Article  CAS  PubMed  Google Scholar 

  22. Sanyal S., Sandstrom D.J., Hoeffer C.A., Ramaswam M. 2002. AP-1 functions upstream of CREB to control synaptic plasticity in Drosophila. Nature. 416, 870–874.

    Article  CAS  PubMed  Google Scholar 

  23. Glyvuk N., Tsytsyura Y., Geumann C., et al. 2010. AP-1/sigma1B-adaptin mediates endosomal synaptic vesicle recycling, learning and memory. EMBO J. 29, 1318–1330.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Horikawa H.P., Kneussel M., El Far O., Betz H. 2002. Interaction of synaptophysin with the AP-1 adaptor protein gamma-adaptin. Mol. Cell. Neurosci. 21, 454–462.

    Article  CAS  PubMed  Google Scholar 

  25. Dwyer N.D., Adler C.E., Crump J.G., L’Etoile N.D., Bargmann C.I. 2001. Polarized dendritic transport and the AP-1 mu1 clathrin adaptor UNC-101 localize odorant receptors to olfactory cilia. Neuron. 31, 277–287.

    Article  CAS  PubMed  Google Scholar 

  26. Ameyar M., Wisniewska M., Weitzman J.B. 2003. A role for AP-1 in apoptosis: The case for and against. Biochimie. 85, 747–752.

    Article  CAS  PubMed  Google Scholar 

  27. Pennypacker K.R. 1995. AP-1 transcription factor complexes in CNS disorders and development. J. Fla. Med. Assoc. 82, 551–554.

    CAS  PubMed  Google Scholar 

  28. Medicherla R., Leers-Sucheta S., Luo Y., Azha S. 2001. Impaired activation of AP-1 and altered expression of constituent proteins in rat adrenal during ageing. Mech. Ageing Dev. 122, 1169–1186.

    Article  CAS  PubMed  Google Scholar 

  29. Smith D.R., Hoyt E.C., Gallagher M., Schwabe R.F., Lund P.K. 2001. Effect of age and cognitive status on basal level AP-1 activity in rat hippocampus. Neurobiol. Aging. 22, 773–786.

    Article  CAS  PubMed  Google Scholar 

  30. Raivich G., Behrens A. 2006. Role of the AP-1 transcription factor c-Jun in developing, adult and injured brain. Prog. Neurobiol. 78, 347–363.

    Article  CAS  PubMed  Google Scholar 

  31. Kyosseva S.V. 2004. Differential expression of mitogenactivated protein kinases and immediate early genes FOS and JUN in thalamus in schizophrenia. Prog. Neuropsychopharmacol. Biol. Psychiatry. 28, 997–1006.

    Article  CAS  PubMed  Google Scholar 

  32. Adcock I.M., Caramori G. 2001. Cross-talk between pro-inflammatory transcription factors and glucocorticoids. Immunol. Cell. Biol. 79, 376–384.

    Article  CAS  PubMed  Google Scholar 

  33. Lee Y.N., Tuckerman J., Nechushtan H., Schutz G., Razin E., Angel P. 2004. c-Fos as a regulator of degranulation and cytokine production in FceRI-activated mast cells. J. Immunol. 173, 2571–2577.

    Article  CAS  PubMed  Google Scholar 

  34. Williams M., Lyu M.S., Yang Y.L., et al. 1999. Ier5, a novel member of the slow-kinetics immediate-early genes. Genomics. 55, 327–334.

    Article  CAS  PubMed  Google Scholar 

  35. Cirelli C. 2002. Functional genomics of sleep and circadian rhythm invited review: How sleep deprivation affects gene expression in the brain: A review of recent findings. J. Appl. Physiol. 92, 394–400.

    CAS  PubMed  Google Scholar 

  36. Savitz J., Frank M. B., Victor T., et al. 2013. Inflammation and neurological disease-related genes are differentially expressed in depressed patients with mood disorders and correlate with morphometric and functional imaging abnormalities. Brain Behav. Immun. 31, 161–171.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. World Health Organization (WHO). 1992. The International Statistical Classification of Diseases and Related Health Problems, 10th ed. Geneve: WHO Publ.

    Google Scholar 

  38. Miller S.A., Dykes D.D., Polesky H.F. 1988. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 16, 1215.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Bunce M., O’Neill C.M., Barnardo M.C., Krausa P., Browning M.J., Morris P.J., Welsh K.I. 1995. Phototyping: Comprehensive DNA typing for HLA-A, B, C, DRB3, DRB4, DRB5, and DQB1 by PCR with 144 primer mixes utilizing sequence-specific primers (PCR-SSP). Tissue Antigens. 46, 355–367.

    Article  CAS  PubMed  Google Scholar 

  40. Lalouel J.M., Rohrwasser A. 2002. Power and replication in case-control studies. Am. J. Hypertens. 15, 201–205.

    Article  PubMed  Google Scholar 

  41. Park H.J., Kim J.W., Cho B.S., Chung J.H. 2014. Association of FOS-like antigen 1 promoter polymorphism with podocyte foot process effacement in immunoglobulin A nephropathy patients. J. Clin. Lab. Anal. 28, 391–397.

    Article  CAS  PubMed  Google Scholar 

  42. Fernández-Rozadilla C., Tarrío R., Clofent J., et al. 2010. Colorectal cancer susceptibility quantitative trait loci in mice as a novel approach to detect low-penetrance variants in humans: A two-stage case-control study. Cancer Epidemiol. Biomarkers Prev. 19, 619–623.

    Article  PubMed  Google Scholar 

  43. de Maturana E.L., Yes Y., Called M.L., et al. 2013. Application of multi-SNP approaches Bayesian LASSO and AUC-RF to detect main effects of inflammatory-gene variants associated with bladder cancer risk. PLOS ONE. 8, e83745.

    Article  PubMed Central  PubMed  Google Scholar 

  44. Yang S.K., Hong M., Zhao W., et al. 2014. Genomewide association study of Crohn’s disease in Koreans revealed three new susceptibility loci and common attributes of genetic susceptibility across ethnic populations. Gut. 63, 80–87.

    Article  CAS  PubMed  Google Scholar 

  45. Yiu W.C., Yap M.K.H., Fung W.Y., Ng P.W., Yip S.P. 2013. Genetic susceptibility to refractive error: Association of vasoactive intestinal peptide receptor 2 (VIPR2) with high myopia in Chinese. PLOS ONE. 8, e61805.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Broyl A., Corthals S.L., Jongen J.L., et al. 2010. Mechanisms of peripheral neuropathy associated with bortezomib and vincristine in patients with newly diagnosed multiple myeloma: A prospective analysis of data from the HOVON-65/GMMG-HD4 trial. Lancet Oncol. 11, 1057–1065.

    Article  CAS  PubMed  Google Scholar 

  47. Kresfelder T.L., Janssen R., Bont L., Pretorius M., Venter M. 2011. Confirmation of an association between single nucleotide polymorphisms in the VDR gene with respiratory syncytial virus related disease in South African children. J. Med. Virol. 83, 1834–1840.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Institute of Molecular Biology, National Academy of Sciences of the Republic of Armenia, Yerevan, 0014, Armenia

    A. S. Boyajyan, S. A. Atshemyan & R. V. Zakharyan

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  1. A. S. Boyajyan
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  2. S. A. Atshemyan
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  3. R. V. Zakharyan
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Correspondence to R. V. Zakharyan.

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Original Russian Text © A.S. Boyajyan, S.A. Atshemyan, R.V. Zakharyan, 2015, published in Molekulyarnaya Biologiya, 2015, Vol. 49, No. 6, pp. 977–983.

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Boyajyan, A.S., Atshemyan, S.A. & Zakharyan, R.V. Association of schizophrenia with variants of genes that encode transcription factors. Mol Biol 49, 875–880 (2015). https://doi.org/10.1134/S0026893315060035

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  • DOI: https://doi.org/10.1134/S0026893315060035

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