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Matrix Metalloproteinase-9 Gene Polymorphisms in South-West Iranian Multiple Sclerosis (MS) Patients

  • HUMAN GENETICS
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Abstract

Background: Matrix metalloproteinases (MMPs) play important role in Multiple Sclerosis (MS), an autoimmune and neuro-inflammatory disease. It has been demonstrated that two important polymorphisms, the –1562 C/T and microsatellite (CA)n near the –90 position in the promoter region of MMP-9 gene are associated with increased MMP-9 expression, through influencing transcriptional process in MS, also some autoimmune diseases as well as cancers. In this study, the possible association of these gene polymorphisms with MS susceptibility, severity as well as age of onset in samples from south-west of Iran were examined. Methods: Polymorphisms for two regions, –1562 C/T (rs3918242) and –90 (CA)n repeat was analyzed in 170 south-west Iranian patients with MS and 200 healthy controls. Results: Results suggested that a genetic polymorphism of the MMP-9 promoter region may influence the susceptibility to MS. Significant increase frequencies of the –1562 T and long (CA)n alleles were found in patients with MS compared to controls. Carriers of two polymorphisms were younger age at disease onset. The disability status of patients, moreover, has been consistently increased by the association of T variants. Conclusion: This study suggests that genotypes and alleles of MMP-9 –1562 C/T gene as well as (CA)n polymorphisms are associated with higher MS susceptibility due to increased MMP-9 protein levels. This finding, therefore, supports the hypothesis of a significant role of this gene in the disease.

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REFERENCES

  1. Block, M.L. and Hong, J., Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism, Prog. Neurobiol., 2005, vol. 76, no. 2, pp. 77–98.

    Article  CAS  Google Scholar 

  2. Hauser, S.L. and Oksenberg, J., The neurobiology of multiple sclerosis: genes, inflammation, and neurodegeneration, Neuron, 2006, vol. 52, no. 1, pp. 61–76.

    Article  CAS  Google Scholar 

  3. Glass, C.K. et al., Mechanisms underlying inflammation in neurodegeneration christopher, Glass, 2010, vol. 140, no. 6, pp. 918–934.

    CAS  Google Scholar 

  4. Hemmer, B., Archelos, J.J., and Hartung, H., New concepts in the immunopathogenesis of multiple sclerosis, Nat. Rev. Neurosci., 2002, vol. 3, no. 4, pp. 291–301.

    Article  CAS  Google Scholar 

  5. Brew, K. and Nagase, H., The tissue inhibitors of metalloproteinases (TIMPs): an ancient family with structural and functional diversity, Biochim. Biophys. Acta—Mol. Cell Res., 2010, vol. 1803, no. 1, pp. 55–71.

    CAS  Google Scholar 

  6. Sbardella, D. et al., Human matrix metalloproteinases: an ubiquitarian class of enzymes involved in several pathological processes, Mol. Aspects Med., 2012, vol. 33, no. 2, pp. 119–208.

    Article  CAS  Google Scholar 

  7. Szabo, K.A., Ablin, R.J., and Singh, G., Matrix metalloproteinases and the immune response, Clin. Appl. Immunol. Rev., 2004, vol. 4, no. 5, pp. 295–319.

    Article  CAS  Google Scholar 

  8. Leppert, D. et al., Matrix metalloproteinases: multifunctional effectors of inflammation in multiple sclerosis and bacterial meningitis, Brain Res. Rev., 2001, vol. 36, nos. 2–3, pp. 249–257.

    Article  CAS  Google Scholar 

  9. Kouwenhoven, M. et al., Multiple sclerosis: elevated expression of matrix metalloproteinases in blood monocytes, J. Autoimmun., 2001, vol. 16, no. 4, pp. 463–470.

    Article  CAS  Google Scholar 

  10. Muir, E.M. et al., Matrix metalloproteases and their inhibitors are produced by overlapping populations of activated astrocytes, Brain Res. Mol. Brain Res., 2002, vol. 100, nos. 1–2, pp. 103–117.

    Article  CAS  Google Scholar 

  11. Sellebjerg, F. and Sørensen, T.L., Chemokines and matrix metalloproteinase-9 in leukocyte recruitment to the central nervous system, Brain Res. Bull., 2003, vol. 61, no. 3, pp. 347–355.

    Article  CAS  Google Scholar 

  12. Avolio, C., et al., Serum MMP-2 and MMP-9 are elevated in different multiple sclerosis subtypes, J. Neuroimmunol., 2003, vol. 136, nos. 1–2, pp. 46–53.

    Article  CAS  Google Scholar 

  13. Boz, C. et al., Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase (TIMP-1) in patients with relapsing–remitting multiple sclerosis treated with interferon beta, Clin. Neurol. Neurosurg., 2006, vol. 108, no. 2, pp. 124–128.

    Article  Google Scholar 

  14. Larochelle, C., Alvarez, J.I., and Prat, A., How do immune cells overcome the blood-brain barrier in multiple sclerosis?, FEBS Lett., 2011, vol. 585, no. 23, pp. 3770–3780.

    Article  CAS  Google Scholar 

  15. Kim, Y.-S. and Joh, T.-H., Matrix metalloproteinases, new insights into the understanding of neurodegenerative disorders, Biomol. Ther., 2012, vol. 20, no. 2, pp. 133–143.

    Article  CAS  Google Scholar 

  16. Brkic, M. et al., Friends or foes: matrix metalloproteinases and their multifaceted roles in neurodegenerative diseases, Mediators Inflamm., 2015, vol. 2015, p. 620581.

    Article  Google Scholar 

  17. Fiotti, N. et al., MMP-9 microsatellite polymorphism and multiple sclerosis, J. Neuroimmunol., 2004, vol. 152, nos. 1–2, pp. 147–153.

    Article  CAS  Google Scholar 

  18. Zivković, M. et al., Matrix metalloproteinase-9 –1562 C/T gene polymorphism in Serbian patients with multiple sclerosis, J. Neuroimmunol., 2007, vol. 189, nos. 1–2, pp. 147–150.

    Article  Google Scholar 

  19. Benešová, Y. et al., Matrix metalloproteinase-9 and matrix metalloproteinase-2 gene polymorphisms in multiple sclerosis, J. Neuroimmunol., 2008, vol. 205, nos. 1–2, pp. 105–109.

    Article  Google Scholar 

  20. Fernandes, K.S.S. et al., Matrix metalloproteinase-9 genotypes and haplotypes are associated with multiple sclerosis and with the degree of disability of the disease, J. Neuroimmunol., 2009, vol. 214, nos. 1–2, pp. 128–131.

    Article  CAS  Google Scholar 

  21. Fernandes, K.S. da S. et al., Functional MMP-9 polymorphisms modulate plasma MMP-9 levels in multiple sclerosis patients, J. Neuroimmunol., 2012, vol. 249, nos. 1–2, pp. 56–59.

    Article  CAS  Google Scholar 

  22. Etemadifar, M. et al., Epidemiology of multiple sclerosis in Iran: a systematic review, Eur. Neurol., 2013, vol. 70, nos. 5–6, pp. 356–363.

    Article  Google Scholar 

  23. Eskandarieh, S. et al., Prevalence and incidence of multiple sclerosis in Tehran, Iran, Iran. J. Public Health, 2017, vol. 46, no. 5, pp. 699.

    PubMed  PubMed Central  Google Scholar 

  24. McDonald, W.I. et al., Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis., Ann. Neurol., 2001, vol. 50, no. 1, pp. 121–127.

    Article  CAS  Google Scholar 

  25. Kurtzke, J.F., Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS), Neurology, 1983, vol. 33, no. 11, pp. 1444.

    Article  CAS  Google Scholar 

  26. Joos, L. et al., The role of matrix metalloproteinase polymorphisms in the rate of decline in lung function., Hum. Mol. Genet., 2002, vol. 11, no. 5, pp. 569–576.

    Article  CAS  Google Scholar 

  27. Rodriguez, S., Gaunt, T.R., and Day, I.N.M., Practice of epidemiology Hardy—Weinberg equilibrium testing of biological ascertainment for Mendelian randomization studies, Am. J. Epidemiol., 2009, vol. 169, no. 4, pp. 505–514.

    Article  Google Scholar 

  28. Rahimi, Z. et al., Functional promoter polymorphisms of MMP-2 C-735T and MMP-9 C-1562T and their synergism with MMP-7 A-181G in multiple sclerosis, Immunol. Invest., 2016, vol. 45, no. 6, pp. 543–552.

    Article  CAS  Google Scholar 

  29. La Russa, A. et al., Single nucleotide polymorphism in the MMP-9 gene is associated with susceptibility to develop multiple sclerosis in an Italian case-control study, J. Neuroimmunol., 2010, vol. 225, nos. 1–2, pp. 175–179.

    Article  CAS  Google Scholar 

  30. Pul, R. et al., Polyclonal immunoglobulins (IVIg) induce expression of MMP-9 in microglia, J. Neuroimmunol., 2009, vol. 217, nos. 1–2, pp. 46–50.

    Article  CAS  Google Scholar 

  31. Aung, L.L. et al., MMP-9 expression is increased in B lymphocytes during multiple sclerosis exacerbation and is regulated by microRNA-320a, J. Neuroimmunol., 2015. vol. 278, pp. 185–189.

    Article  CAS  Google Scholar 

  32. Comabella, M. et al., Changes in matrix metalloproteinases and their inhibitors during interferon-beta treatment in multiple sclerosis, Clin. Immunol., 2009, vol. 130, no. 2, pp. 145–150.

    Article  CAS  Google Scholar 

  33. Shinto, L. et al., Omega-3 fatty acid supplementation decreases matrix metalloproteinase-9 production in relapsing-remitting multiple sclerosis, Prostaglandins, Leukotrienes Essent. Fat. Acids, 2009, vol. 80, nos. 2–3, pp. 131—136.

    Article  CAS  Google Scholar 

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ACKNOWLEDGMENTS

The authors would like to thank all the participants for taking part in this study and especially Genetic Department of Shahid Chamran University of Ahvaz and Khuzestan Province MS Society of the Jundishapur Hospital for supporting this project. The authors wish to appreciate Dr. Leila Heidarvand for comments and suggestions on manuscript improvement.

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Authors and Affiliations

  1. Department of Genetics, Faculty of Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran

    N. Kh. S. Sadr, H. Galehdari, T. Seifi, N. Delfan, S. R. Khatami & A. Hafizi

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  1. N. Kh. S. Sadr
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  2. H. Galehdari
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  3. T. Seifi
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  4. N. Delfan
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Correspondence to N. Kh. S. Sadr or H. Galehdari.

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Conflict of interests. The authors declare that there is no conflict of interests regarding the publication of this paper.

Statement of compliance with standards of research involving humans as subjects. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent was obtained from all individual participants included in the study.

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Sadr, N.K., Galehdari, H., Seifi, T. et al. Matrix Metalloproteinase-9 Gene Polymorphisms in South-West Iranian Multiple Sclerosis (MS) Patients. Russ J Genet 55, 1266–1272 (2019). https://doi.org/10.1134/S1022795419100107

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  • DOI: https://doi.org/10.1134/S1022795419100107

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