MATRIX METALLOPROTEINASES -3 (MMP-3) SERUM LEVEL AND GENETIC POLYMORPHISMS ASSOCIATED WITH RHEUMATOID ARTHRITIS



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Abstract

Abstract

Introduction: MMP3 plays a crucial role in the process of bone erosion in the pathomechanism of rheumatoid arthritis (RA). It acts by removing the outer osteoid layer, which allows the osteoclasts to tightly connect and carry out the subsequent damage to the underlying bone. MMP3 can trigger the production of other MMPs like MMP-1, MMP-7, and MMP-9, it plays a pivotal role in the remodeling of connective tissues.

Aim of the study: to assess the influence of MMP-3 serum levels and single-nucleotide polymorphisms of rs679620 in the rheumatoid arthritis patients' group in comparison to the control group.

Subjects: eighty eight samples, 45 rheumatoid arthritis patients after being referred by their treating physician for regular RA test. The remaining 43 samples all represent apparently healthy people. The present study investigated the serum concentration of MMP-3 and rs679620 SNPs in the group of patients with RA, in comparison to the control group.

Results: The results indicated a significant elevation in MMP-3 levels in  RA patients in comparison to healthy individuals (12.75 ± 0.38 vs. 9.69 ± 0.37) and the findings of  rs679620 SNPs appeared that the patient group has a non-significant increase in both allele frequency A and genotype frequency AA when compared to the control group (66.2 vs. 52.2 %; p = 0.172; OR = 1.79 and 35.3 vs. 17.4 %; p = 0.229; OR = 2.59) , but a non-significant decrease in both allele frequency C and genotype frequency CC when compared to the control group (2.94 vs. 4.4 %; p = 1.0; OR = 0.67 and 2.9 vs. 4.3 %; p = 1.0; OR = 0.67), as well as a non-significant decrease in allele frequency G and both genotypes frequency GG and AG when compared to the control group (30.9 vs. 43.5 %; p = 0.233; OR = 0.58, 0.0 vs. 8.7 %; p = 0.159; OR = 0.12 and 61.8 vs. 69.6 %; p = 0.585; OR = 0.71 ). Patients carrying the AA and AG genotype, had significantly higher serum levels of MMP-3 compared to control (P= 0.005 and 0.004) respectively.

Conclusion: Rs679620 may influence joint destruction via increase MMP-3 production.

About the authors

Wafaa Ayad Al-nuaimy

Baghdad University, Baghdad, Iraq

Email: wafaa.ayad@mu.edu.iq

Master in science, phd candidate.     College of Science  / Baghdad University / Baghdad /Iraq

Iraq

Dunya Fareed Salloom

College of Science, Baghdad University, Baghdad, Iraq

Author for correspondence.
Email: dunyascience@sc.uobaghdad.edu.iq

Doctor, Professor, Supervisor. College of Science / Baghdad University / Baghdad /Iraq

Iraq

References

  1. Abramson JH. WINPEPI updated: computer programs for epidemiologists, and their teaching potential. Epidemiol Perspect Innov. 2011 Feb 2;8(1):1. doi: 10.1186/1742-5573-8-1. PMID: 21288353; PMCID: PMC3041648.
  2. Ahmed. DM and Salloom. DF. The Association between Toll-like Receptor 7 and Hepatitis C Virus in a Sample of Iraqi Rheumatoid Arthritis Patients. Journal of Global Pharma Technology. (2 018).Vol. 10 | Issue 11 (Suppl.) |01-08
  3. Al-Derzi AR. The Contribution of Serum Anti–cyclic Citrullinated Peptide Antibody and Matrix Metalloproteinase-3 in Predicting the Activity of Rheumatoid Arthritis Disease. J.Fac.Med.Bagdad . 2017. 8;59(2):138-44. https://doi.org/10.32007/jfacmedbagdad.592124
  4. Andrews, C., 2010. The Hardy-Weinberg principle. Nat. Educ. Knowl. 3 (10), 65.
  5. Burrage PS, Mix KS, Brinckerhoff CE. Matrix metalloproteinases: role in arthritis. Front Biosci. 2006 Jan 1;11:529-43. doi: 10.2741/1817. PMID: 16146751.
  6. Cabral-Pacheco GA, Garza-Veloz I, Castruita-De la Rosa C, Ramirez-Acuña JM, Perez-Romero BA, Guerrero-Rodriguez JF, Martinez-Avila N, Martinez-Fierro ML. The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases. Int J Mol Sci. 2020 Dec 20;21(24):9739. doi: 10.3390/ijms21249739. PMID: 33419373; PMCID: PMC7767220.
  7. Chen, Y., Nixon, N., Dawes, P. et al. Influence of variations across the MMP-1 and -3 genes on the serum levels of MMP-1 and -3 and disease activity in rheumatoid arthritis. Genes Immun 13, 29–37 (2012). https://doi.org/10.1038/gene.2011.46
  8. du Teil Espina M, Gabarrini G, Harmsen HJM, Westra J, van Winkelhoff AJ, van Dijl JM. Talk to your gut: the oral-gut microbiome axis and its immunomodulatory role in the etiology of rheumatoid arthritis. FEMS Microbiol Rev. 2019 Jan 1;43(1):1-18. doi: 10.1093/femsre/fuy035. PMID: 30219863.
  9. Fadda,S. Abolkheir,E. Afifi,R. Gamal, M. Serum matrix metalloproteinase-3 in rheumatoid arthritis patients: Correlation with disease activity and joint destruction, The Egyptian Rheumatologist, Volume 38, Issue 3, 2016, Pages 153-159. https://doi.org/10.1016/j.ejr.2016.01.001
  10. Galil SM, El-Shafey AM, Hagrass HA, Fawzy F, Sammak AE. Baseline serum level of matrix metalloproteinase-3 as a biomarker of progressive joint damage in rheumatoid arthritis patients. Int J Rheum Dis. 2016 Apr;19(4):377-84. doi: 10.1111/1756-185X.12434. Epub 2014 Oct 7. PMID: 25292349.
  11. Hamid. ZA. (2017). The Impact of Hepatitis B Virus and Epstein Barr Virus in Pathogenesis of Rheumatoid Arthritis. Biomedical & Pharmacology Journal. Vol. 10(3), 1495-1501. doi.org/10.13005/bpj/1258.
  12. Ismael. MK; Aldabagh. MA; Rasuol. LM. Matrix Metalloproteinase-3 and Tissue inhibitor of metalloproteinase-2 as Diagnostic Markers for COVID-19 Infection. Iraqi Journal of Science, 2022, Vol. 63, No. 9, pp: 3679-3687 doi: 10.24996/ijs.2022.63.9.2
  13. Jassim. N.S, Aboud. R.S, Joda. A.T. Detection of Epstein - Barr virus Capsid antigen (EBV CA) in Sera of Rheumatoid Arthritis, Reactive Arthritis and Ankylosing Spondylitis Patients. Iraqi Journal of Science (2015). Vol 56, No.4B, pp: 3130-3134. https://ijs. uobaghdad.edu.iq/index.php/eijs/article/ view/ 9385.
  14. Jonsson A, Hjalmarsson C, Falk P, Ivarsson ML. Levels of matrix metalloproteinases differ in plasma and serum - aspects regarding analysis of biological markers in cancer. Br J Cancer. 2016 Sep 6;115(6):703-6. doi: 10.1038/bjc.2016.127. Epub 2016 May 17. PMID: 27187685; PMCID: PMC5023769.
  15. Khamaes, E. S., Al-Bayati, N. Y., & Abbas, A. H. (2022). Tissue inhibitor of metalloproteinase-1 (TIMP-1) serum level and genetic polymorphisms associated with cutaneous leishmania infections. Human Gene, 33, 201049.‏ doi: 10.1016/j.humgen.2022.201049
  16. Khayon. LH ; Farhan. AA ; Salloom. DF. Association of Interleukin-12B Polymorphism and Serum Level of Interleukin-12 in a Sample of Iraqi Patients with Rheumatoid Arthritis. The Egyptian Journal of Hospital Medicine. (2023).Volume 90, Issue 2. Page 2071-2073 doi: 10.21608/EJHM.2023.285034.
  17. Lerner A, Neidhöfer S, Reuter S, Matthias T. MMP3 is a reliable marker for disease activity, radiological monitoring, disease outcome predictability, and therapeutic response in rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2018 Aug;32(4):550-562. doi: 10.1016/j.berh.2019.01.006. Epub 2019 Feb 14. PMID: 31174824.
  18. Liang Z, Wang N, Shang L, Wang Y, Feng M, Liu G, Gao C, Luo J. Evaluation of the immune feature of ACPA-negative rheumatoid arthritis and the clinical value of matrix metalloproteinase-3. Front Immunol. 2022 Jul 27;13:939265. doi: 10.3389/fimmu.2022.939265. PMID: 35967336; PMCID: PMC9363571.
  19. Ma JD, Zhou JJ, Zheng DH, Chen LF, Mo YQ, Wei XN, Yang LJ, Dai L. Serum matrix metalloproteinase-3 as a noninvasive biomarker of histological synovitis for diagnosis of rheumatoid arthritis. Mediators Inflamm. 2014;2014:179284. doi: 10.1155/2014/179284. Epub 2014 Jul 23. PMID: 25147433; PMCID: PMC4132319.
  20. Mohammed, H and Salloom,DF. Evaluation of interleukin-9 serum level and gene polymorphism in a sample of Iraqi type 2 diabetic mellitus patient. Meta Gene.(2021).Volume 27,, 100845 ISSN 2214-5400, https://doi.org/10.1016/j.mgene.2020.100845.
  21. Sabnis, R. W. “Handbook of biological dyes and stains: synthesis and industrial application‖.Hoboken,N.J.:Wiley.(2010).
  22. Salloom. DF; Fadhil. HY and Abbas. AH. Evaluation of leptin in sera of a sample of rheumatoid arthritis of iraqi patients. International journal of recent scientific research.(2013). 4 (4), 004 – 005
  23. Thaer K, Abdulla BH; Kadhim KR. Immunohistochemical expression of MMP9, as a marker of local invasion in Hodgkin’s and Non-Hodgkin’s lymphoma of the head and neck region. J Bagh Coll Dent . 2015 Mar. 27(1):128-32.
  24. Wang X, Khalil RA. Matrix Metalloproteinases, Vascular Remodeling, and Vascular Disease. Adv Pharmacol. 2018;81:241-330. doi: 10.1016/bs.apha.2017.08.002. Epub 2017 Sep 19. PMID: 29310800; PMCID: PMC5765875.
  25. Wu H, Liao W, Li Q, Long H, Yin H, Zhao M, Chan V, Lau CS, Lu Q. Pathogenic role of tissue-resident memory T cells in autoimmune diseases. Autoimmun Rev. 2018 Sep;17(9):906-911. doi: 10.1016/j.autrev.2018.03.014. Epub 2018 Jul 10. PMID: 30005862.

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