Hostname: page-component-586b7cd67f-g8jcs Total loading time: 0 Render date: 2024-11-27T20:08:14.409Z Has data issue: false hasContentIssue false
  • English
  • Français

How matrix metalloproteinase (MMP)-9 (rs3918242) polymorphism affects MMP-9 serum concentration and associates with autism spectrum disorders: A case-control study in Iranian population

Published online by Cambridge University Press:  01 February 2021

Javid Rezaei Lord ,
Farhad Mashayekhi Open the ORCID record for Farhad Mashayekhi [Opens in a new window]  and
Zivar Salehi
Javid Rezaei Lord*
Affiliation:
Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Guilan, Iran
Farhad Mashayekhi
Affiliation:
Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Guilan, Iran
Zivar Salehi
Affiliation:
Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Guilan, Iran
*
Author for Correspondence: Farhad Mashayekhi, University of Guilan, Rasht, Guilan, Iran; E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

The aim of this project was to evaluate the relationship of matrix metalloproteinase-9 (MMP-9) genetic variation and its serum concentration with autism spectrum disorder (ASD). One hundred ASD and 120 controls were enrolled in this study. Genomic DNA was extracted from blood and MMP-9 polymorphism was determined by polymerase chain reaction restriction fragment length polymorphism and serum levels were measured by enzyme-linked immunosorbent assay. The frequencies of CC, CT, and TT genotypes were 72%, 26%, and 2% in controls and 31%, 57%, and 12% in ASD, respectively. The frequencies of C and T alleles in ASD were 59.5% and 40.5%, and controls were 86% and 14%, respectively. There is a significant increase in serum MMP-9 levels in ASD as compared to controls. We have also shown that TT genotype is significantly associated with increase serum MMP-9 levels in patients (TT, CT, and CC serum levels were 91.77 ± 10.53, 70.66 ± 7.21, and 38.66 ± 5.52 and in controls were 55.55 ± 11.39, 42.66 ± 7.85, and 30.55 ± 6.34 ng/ml, respectively). It is concluded that there is a significant association between rs3918242 MMP-9 polymorphism and its serum concentration with autism. We also suggest that TT genotype is associated with increased MMP9 expression and may be a risk factor for ASD.

Keywords

autism spectrum disordersgene polymorphismMMP-9serum
Type
Regular Article
Information
Development and Psychopathology , Volume 34 , Issue 3 , August 2022 , pp. 882 - 888
Check for updates
Copyright
© The Author(s), 2021. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abdallah, M. W., & Michel, T. M. (2013). Matrix metalloproteinases in autism spectrum disorders. Journal of Molecular Psychiatry, 1, 16.CrossRefGoogle ScholarPubMed
Barkhash, A. V., Yurchenko, A. A., Yudin, N. S., Ignatieva, E. V., Kozlova, I. V., Borishchuk, I. A., … Romaschenko, A. G. (2018). A matrix metalloproteinase 9 (MMP9) gene single nucleotide polymorphism is associated with predisposition to tick-borne encephalitis virus-induced severe central nervous system disease. Ticks and Tick-Borne Diseases, 9, 763–767.CrossRefGoogle ScholarPubMed
Barr, T. L., Latour, L. L., Lee, K. Y., Schaewe, T. J., Luby, M., Chang, G. S., … Warach, S. (2010). Blood-brain barrier disruption in humans is independently associated with increased matrix metalloproteinase-9. Stroke, 41, e123–e128.CrossRefGoogle ScholarPubMed
Bronisz, E., & Kurkowska-Jastrzębska, I. (2016). Matrix metalloproteinase 9 in epilepsy: The role of neuroinflammation in seizure development. Mediators of Inflammation, 2016, 7369020.CrossRefGoogle ScholarPubMed
Buraczynska, K., Kurzepa, J., Ksiazek, A., Buraczynska, M., & Rejdak, K. (2015). Matrix metalloproteinase-9 (MMP-9 ) gene polymorphism in stroke patients. Neuromolecular Medicine, 17, 385–390.CrossRefGoogle ScholarPubMed
Chiu, P. S., & Lai, S. C. (2014). Matrix metalloproteinase-9 leads to blood-brain barrier leakage in mice with eosinophilic meningoencephalitis caused by angiostrongylus cantonensis. Acta Tropica, 140, 141–150.CrossRefGoogle ScholarPubMed
Delshadpour, M., Mashayekhi, F., Bidabadi, E., Shahangian, S., & Salehi, Z. (2017). MTHFR rs1801133 gene polymorphism and autism susceptibility. Caspian Journal of Neurological Sciences, 3, 39–45.Google Scholar
del Zoppo, G. J., Milner, R., Mabuchi, T., Hung, S., Wang, X., Berg, G. I., … Koziol, J. A. (2007). Microglial activation and matrix protease generation during focal cerebral ischemia. Stroke, 38, 646–651.CrossRefGoogle ScholarPubMed
Ethell, I. M., & Ethell, D. W. (2007). Matrix metalloproteinases in brain development and remodeling: Synaptic functions and targets. Journal of Neuroscience Research, 85, 2813–2823.CrossRefGoogle ScholarPubMed
Farina, A. R., & Mackay, A. R. (2014). Gelatinase B/MMP-9 in tumour pathogenesis and progression. Cancers, 6, 240–296.CrossRefGoogle ScholarPubMed
Fiorentino, M., Sapone, A., Senger, S., Camhi, S. S., Kadzielski, S. M., Buie, T. M., … Fasano, A. (2016). Blood-brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders. Molecular Autism, 7, 49.CrossRefGoogle ScholarPubMed
Frazier, T. W., Youngstrom, E. A., Speer, L., Embacher, R., Law, P., Constantino, J., … Eng, C. (2012). Validation of proposed DSM-5 criteria for autism spectrum disorder. Journal of the American Academy of Child & Adolescent Psychiatry, 51, 28–40.Google ScholarPubMed
Fujiwara, T., Morisaki, N., Honda, Y., Sampei, M., & Tani, Y. (2016). Chemicals, nutrition, and autism spectrum disorder: A mini-review. Frontiers in Neuroscience, 10, 174.CrossRefGoogle ScholarPubMed
Gao, N., Guo, T., Luo, H., Tu, G., Niu, F., Yan, M., … Xia, Y. (2019). Association of the MMP-9 polymorphism and ischemic stroke risk in southern Chinese Han population. BMC Neurology, 19, 67.CrossRefGoogle ScholarPubMed
Gentile, I., Zappulo, E., Riccio, M. P., Binda, S., Bubba, L., Pellegrinelli, L., … Bravaccio, C. (2017). Prevalence of congenital cytomegalovirus infection assessed through viral genome detection in dried blood spots in children with autism spectrum disorders. In Vivo, 31, 467–473.CrossRefGoogle ScholarPubMed
Glebauskiene, B., Liutkeviciene, R., Vilkeviciute, A., Kriauciuniene, L., Jakstiene, S., Zlatkute, E., … Zaliuniene, D. (2017). Does MMP-9 gene polymorphism play a role in pituitary adenoma development? Disease Markers, 2017, 5839528.CrossRefGoogle ScholarPubMed
Gurau, O., Bosl, W. J., & Newton, C. R. (2017). How useful is electroencephalography in the diagnosis of autism spectrum disorders and the delineation of subtypes: A systematic review. Frontiers in Psychiatry, 8, 121.CrossRefGoogle Scholar
Haghiri, R., Mashayekhi, F., Bidabadi, E., & Salehi, Z. (2016). Analysis of methionine synthase (rs1805087) gene polymorphism in autism patients in Northern Iran. Acta Neurobiologiae Experimentalis, 76, 318–323.CrossRefGoogle ScholarPubMed
He, T., Wang, J., Wang, X. L., Deng, W. S., & Sun, P. (2017). Association between the matrix metalloproteinase-9 rs3918242 polymorphism and ischemic stroke susceptibility: A meta-analysis. Journal of Stroke and Cerebrovascular Diseases, 26, 1136–1143.CrossRefGoogle ScholarPubMed
Hosseinpour, M., Mashayekhi, F., Bidabadi, E., & Salehi, Z. (2017). Neuropilin-2 rs849563 gene variations and susceptibility to autism in Iranian population: A case-control study. Metabolic Brain Disease, 32, 1471–1474.CrossRefGoogle ScholarPubMed
Kadziela-Olech, H., Cichocki, P., Chwiesko, J., Konstantynowicz, J., & Braszko, J. J. (2015). Serum matrix metalloproteinase-9 levels and severity of symptoms in boys with attention deficit hyperactivity disorder ADHD/hyperkinetic disorder HKD. European Child & Adolescent Psychiatry, 24, 55–63.CrossRefGoogle ScholarPubMed
Kandagaddala, L. D., Kang, M. J., Chung, B. C., Patterson, T. A., & Kwon, O. S. (2012). Expression and activation of matrix metalloproteinase-9 and NADPH oxidase in tissues and plasma of experimental autoimmune encephalomyelitis in mice. Experimental and Toxicologic Pathology, 64, 109–114.CrossRefGoogle ScholarPubMed
Laplante, D. P., Simcock, G., Cao-Lei, L., Mouallem, M., Elgbeili, G., Brunet, A., … King, S. (2019). The 5-HTTLPR polymorphism of the serotonin transporter gene and child's sex moderate the relationship between disaster-related prenatal maternal stress and autism spectrum disorder traits: The QF2011 Queensland flood study. Development and Psychopathology, 31, 1395–1409.CrossRefGoogle ScholarPubMed
Lepeta, K., & Kaczmarek, L. (2015). Matrix metalloproteinase-9 as a novel player in synaptic plasticity and schizophrenia. Schizophrenia Bulletin, 41, 1003–1009.CrossRefGoogle ScholarPubMed
Lu, Z., Cao, Y., Wang, Y., Zhang, Q., Zhang, X., Wang, S., … Zhang, J. (2007). Polymorphisms in the matrix metalloproteinase-1, 3, and 9 promoters and susceptibility to adult astrocytoma in northern China. Journal of Neuro-Oncology, 85, 65–73.CrossRefGoogle ScholarPubMed
Niu, B., Li, F., Xiong, Y., & Wang, X. (2013). Characterization and association analysis with litter size traits of porcine matrix metalloproteinase-9 gene (pMMP-9 ). Applied Biochemistry and Biotechnology, 171, 786–794.CrossRefGoogle Scholar
Ornoy, A., Weinstein-Fudim, L., & Ergaz, Z. (2016). Genetic syndromes, maternal diseases and antenatal factors associated with autism spectrum disorders (ASD). Frontiers in Neuroscience, 10, 316.CrossRefGoogle Scholar
Power, C., Henry, S., Del Bigio, M. R., Larsen, P. H., Corbett, D., Imai, Y., … Peeling, J. (2002). Intracerebral hemorrhage induces macrophage activation and matrix metalloproteinases. Annals of Neurology, 53, 731–742.CrossRefGoogle Scholar
Ramsey, J. M., Guest, P. C., Broek, J. A., Glennon, J. C., Rommelse, N., Franke, B., … Bahn, S. (2013). Identification of an age-dependent biomarker signature in children and adolescents with autism spectrum disorders. Molecular Autism, 4, 27.CrossRefGoogle ScholarPubMed
Reinhard, S. M., Razak, K., & Ethell, I. M. (2015). A delicate balance: Role of MMP-9 in brain development and pathophysiology of neurodevelopmental disorders. Frontiers in Cellular Neuroscience, 9, 280.CrossRefGoogle ScholarPubMed
Rempe, R. G., Hartz, A. M. S., & Bauer, B. (2016). Matrix metalloproteinases in the brain and blood-brain barrier: Versatile breakers and makers. Journal of Cerebral Blood Flow & Metabolism, 36, 1481–1507.CrossRefGoogle ScholarPubMed
Romi, F., Helgeland, G., & Gilhus, N. E. (2012). Serum levels of matrix metalloproteinases: Implications in clinical neurology. European Neurology, 67, 121–128.CrossRefGoogle ScholarPubMed
Rosenberg, G. A., & Yang, Y. (2007). Vasogenic edema due to tight junction disruption by matrix metalloproteinases in cerebral ischemia. Neurosurg Focus, 22, E4.CrossRefGoogle ScholarPubMed
Saftig, P., & Bovolenta, P. (2015). Proteases at work: Cues for understanding neural development and degeneration. Frontiers in Molecular Neuroscience, 8, 13.CrossRefGoogle ScholarPubMed
Sandoval, K. E., & Witt, K. A. (2008). Blood-brain barrier tight junction permeability and ischemic stroke. Neurobiology of Disease, 32, 200–219.CrossRefGoogle ScholarPubMed
Singh, H., Nain, S., Krishnaraj, A., Lata, S., & Dhole, T. N. (2019). Genetic variation of matrix metalloproteinase enzyme in HIV-associated neurocognitive disorder. Gene, 698, 41–49.CrossRefGoogle ScholarPubMed
Stawarski, M., Stefaniuk, M., & Wlodarczyk, J. (2014). Matrix metalloproteinase-9 involvement in the structural plasticity of dendritic spines. Frontiers in Neuroanatomy, 8, 68.CrossRefGoogle ScholarPubMed
Vafadari, B., Salamian, A., & Kaczmarek, L. (2016). MMP-9 in translation: From molecule to brain physiology, pathology, and therapy. Journal of Neurochemistry, 139, 91–114.CrossRefGoogle Scholar
Valado, A., Leitão, M. J., Martinho, A., Pascoal, R., Cerqueira, J., Correia, I., … Baldeiras, I. (2017). Multiple sclerosis: Association of gelatinase B/matrix metalloproteinase-9 with risk and clinical course the disease. Multiple Sclerosis and Related Disorders, 11, 71–76.CrossRefGoogle ScholarPubMed
Wen, T. H., Binder, D. K., Ethell, I. M., & Razak, K. A. (2018). The perineuronal “safety” Net? Perineuronal Net abnormalities in neurological disorders. Frontiers in Molecular Neuroscience, 11, 270.CrossRefGoogle ScholarPubMed
Werling, D. M., & Geschwind, D. H. (2013). Sex differences in autism spectrum disorders. Current Opinion in Neurology, 26, 146–153.CrossRefGoogle ScholarPubMed
Xu, Y., Wang, Y., Zhi, J., Qi, L., Zhang, T., & Li, X. (2017). Impact of matrix metalloproteinase 9 rs3918242 genetic variant on lipid-lowering efficacy of simvastatin therapy in Chinese patients with coronary heart disease. BMC Pharmacology and Toxicology, 18, 28.CrossRefGoogle ScholarPubMed
Young, G. S., Merin, N., Rogers, S. J., & Ozonoff, S. (2009). Gaze behavior and affect at 6 months: Predicting clinical outcomes and language development in typically developing infants and infants at risk for autism. Developmental Science, 12, 798–814.CrossRefGoogle ScholarPubMed
Zare, S., Mashayekhi, F., & Bidabadi, E. (2017). The association of CNTNAP2 rs7794745 gene polymorphism and autism in Iranian population. Journal of Clinical Neuroscience, 39, 189–192.CrossRefGoogle ScholarPubMed
Zhong, C., Bu, X., Xu, T., Guo, L., Wang, X., Zhang, J., & Chen, C. S. (2018). Serum matrix metalloproteinase-9 and cognitive impairment after acute ischemic stroke. Journal of the American Heart Association, 7, e007776.Google ScholarPubMed