Skip to main content

Advertisement

Log in

MMP-2, TNF-α and NLRP1 polymorphisms in Chinese patients with ankylosing spondylitis and rheumatoid arthritis

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are autoimmune, inflammatory diseases with substantial genetic contributions. Matrix metalloproteinase (MMP)-2, tumor necrosis factor (TNF)-α and NLR family pyrin domain-containing 1 (NLRP1) play important roles in the immune response. We studied the MMP-2 rs243865 C/T, TNF-α rs1800629 A/G, NLRP1 rs878329 C/G and NLRP1 rs6502867 C/T polymorphisms in a Chinese cohort of 520 patients with RA, 100 with AS and 520 controls. Genotyping was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Using the MMP-2 rs243865 CC homozygote genotype as the reference group, the CT and TT/CT genotypes were associated with significantly reduced risks of AS. However, logistic regression analyses revealed that the MMP-2 rs243865 C/T polymorphism was not associated with risk of RA. TNF-α rs1800629 A/G, NLRP1 rs878329 C/G and NLRP1 rs6502867 C/T polymorphisms were not associated with risk of RA or AS. These findings suggest that the MMP-2 rs243865 C/T polymorphism is associated with AS development.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

CI:

Confidence interval

LD:

Linkage disequilibrium

MMP-2:

Matrix metalloproteinase-2

NLRP1:

NLR family pyrin domain-containing 1

OR:

Odds ratio

SNP:

Single nucleotide polymorphism

TNF-α:

Tumor necrosis factor-α

References

  1. Braun J, Sieper J (2007) Ankylosing spondylitis. Lancet 369:1379–1390

    Article  PubMed  Google Scholar 

  2. Plenge RM, Seielstad M, Padyukov L et al (2007) TRAF1-C5 as a risk locus for rheumatoid arthritis—a genomewide study. N Engl J Med 357:1199–1209

    Article  PubMed  CAS  Google Scholar 

  3. Giannelli G, Erriquez R, Iannone F et al (2004) MMP-2, MMP-9, TIMP-1 and TIMP-2 levels in patients with rheumatoid arthritis and psoriatic arthritis. Clin Exp Rheumatol 22:335–338

    PubMed  CAS  Google Scholar 

  4. Parks WC, Wilson CL, Lopez-Boado YS (2004) Matrix metalloproteinases as modulators of inflammation and innate immunity. Nat Rev Immunol 4:617–629

    Article  PubMed  CAS  Google Scholar 

  5. Huang H, Zhao W, Tang Z et al (2009) Characterization of porcine MMP-2 and its association with immune traits. Gene 435:63–71

    Article  PubMed  CAS  Google Scholar 

  6. Yoshihara Y, Nakamura H, Obata K et al (2000) Matrix metalloproteinases and tissue inhibitors of metalloproteinases in synovial fluids from patients with rheumatoid arthritis or osteoarthritis. Ann Rheum Dis 59:455–461

    Article  PubMed  CAS  Google Scholar 

  7. Konttinen YT, Ainola M, Valleala H et al (1999) Analysis of 16 different matrix metalloproteinases (MMP-1 to MMP-20) in the synovial membrane: different profiles in trauma and rheumatoid arthritis. Ann Rheum Dis 58:691–697

    Article  PubMed  CAS  Google Scholar 

  8. Hot A, Zrioual S, Lenief V, Miossec P (2012) IL-17 and tumour necrosis factor alpha combination induces a HIF-1alpha-dependent invasive phenotype in synoviocytes. Ann Rheum Dis 71:1393–1401

    Article  PubMed  CAS  Google Scholar 

  9. Itoh T, Matsuda H, Tanioka M et al (2002) The role of matrix metalloproteinase-2 and matrix metalloproteinase-9 in antibody-induced arthritis. J Immunol 169:2643–2647

    PubMed  CAS  Google Scholar 

  10. Corry DB, Rishi K, Kanellis J et al (2002) Decreased allergic lung inflammatory cell egression and increased susceptibility to asphyxiation in MMP2-deficiency. Nat Immunol 3:347–353

    Article  PubMed  CAS  Google Scholar 

  11. Li G, Zhang Y, Qian Y et al (2013) Interleukin-17A promotes rheumatoid arthritis synoviocytes migration and invasion under hypoxia by increasing MMP2 and MMP9 expression through NF-kappaB/HIF-1alpha pathway. Mol Immunol 53:227–236

    Article  PubMed  CAS  Google Scholar 

  12. Price SJ, Greaves DR, Watkins H (2001) Identification of novel, functional genetic variants in the human matrix metalloproteinase-2 gene: role of Sp1 in allele-specific transcriptional regulation. J Biol Chem 276:7549–7558

    Article  PubMed  CAS  Google Scholar 

  13. Chang YH, Lin IL, Tsay GJ et al (2008) Elevated circulatory MMP-2 and MMP-9 levels and activities in patients with rheumatoid arthritis and systemic lupus erythematosus. Clin Biochem 41:955–959

    Article  PubMed  CAS  Google Scholar 

  14. Hitchon CA, Danning CL, Illei GG, El-Gabalawy HS, Boumpas DT (2002) Gelatinase expression and activity in the synovium and skin of patients with erosive psoriatic arthritis. J Rheumatol 29:107–117

    PubMed  CAS  Google Scholar 

  15. Nell VP, Machold KP, Eberl G et al (2004) Benefit of very early referral and very early therapy with disease-modifying anti-rheumatic drugs in patients with early rheumatoid arthritis. Rheumatology (Oxford) 43:906–914

    Article  CAS  Google Scholar 

  16. Lee YH, Bae SC, Choi SJ, Ji JD, Song GG (2012) Genome-wide pathway analysis of genome-wide association studies on systemic lupus erythematosus and rheumatoid arthritis. Mol Biol Rep 39(12):10627–10635

    Article  PubMed  CAS  Google Scholar 

  17. Bouma G, Crusius JB, Oudkerk Pool M et al (1996) Secretion of tumour necrosis factor alpha and lymphotoxin alpha in relation to polymorphisms in the TNF genes and HLA-DR alleles. Relevance for inflammatory bowel disease. Scand J Immunol 43:456–463

    Article  PubMed  CAS  Google Scholar 

  18. Louis E, Franchimont D, Piron A et al (1998) Tumour necrosis factor (TNF) gene polymorphism influences TNF-alpha production in lipopolysaccharide (LPS)-stimulated whole blood cell culture in healthy humans. Clin Exp Immunol 113:401–406

    Article  PubMed  CAS  Google Scholar 

  19. Martinon F, Burns K, Tschopp J (2002) The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell 10:417–426

    Article  PubMed  CAS  Google Scholar 

  20. Jin Y, Mailloux CM, Gowan K et al (2007) NALP1 in vitiligo-associated multiple autoimmune disease. N Engl J Med 356:1216–1225

    Article  PubMed  CAS  Google Scholar 

  21. Jin Y, Birlea SA, Fain PR, Spritz RA (2007) Genetic variations in NALP1 are associated with generalized vitiligo in a Romanian population. J Invest Dermatol 127:2558–2562

    Article  PubMed  CAS  Google Scholar 

  22. Jin Y, Riccardi SL, Gowan K, Fain PR, Spritz RA (2010) Fine-mapping of vitiligo susceptibility loci on chromosomes 7 and 9 and interactions with NLRP1 (NALP1). J Invest Dermatol 130:774–783

    Article  PubMed  CAS  Google Scholar 

  23. Magitta NF, Boe Wolff AS, Johansson S et al (2009) A coding polymorphism in NALP1 confers risk for autoimmune Addison’s disease and type 1 diabetes. Genes Immun 10:120–124

    Article  PubMed  CAS  Google Scholar 

  24. Sui J, Li H, Fang Y et al (2012) NLRP1 gene polymorphism influences gene transcription and is a risk factor for rheumatoid arthritis in han chinese. Arthritis Rheum 64:647–654

    Article  PubMed  CAS  Google Scholar 

  25. Arnett FC, Edworthy SM, Bloch DA et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324

    Article  PubMed  CAS  Google Scholar 

  26. van der Linden S, Valkenburg HA, Cats A (1984) Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 27:361–368

    Article  PubMed  Google Scholar 

  27. Cheng J, Zhang H, Zhuang C, Liu R (2012) Peptidylarginine deiminase type 4 and methyl-CpG binding domain 4 polymorphisms in Chinese patients with rheumatoid arthritis. J Rheumatol 39:1159–1165

    Article  PubMed  CAS  Google Scholar 

  28. Veidal SS, Larsen DV, Chen X et al (2012) MMP mediated type V collagen degradation (C5 M) is elevated in ankylosing spondylitis. Clin Biochem 45:541–546

    Article  PubMed  CAS  Google Scholar 

  29. Yu C, Zhou Y, Miao X et al (2004) Functional haplotypes in the promoter of matrix metalloproteinase-2 predict risk of the occurrence and metastasis of esophageal cancer. Cancer Res 64:7622–7628

    Article  PubMed  CAS  Google Scholar 

  30. Saracini C, Bolli P, Sticchi E et al (2012) Polymorphisms of genes involved in extracellular matrix remodeling and abdominal aortic aneurysm. J Vasc Surg 55:171–179

    Article  PubMed  Google Scholar 

  31. Peng B, Cao L, Ma X et al (2010) Meta-analysis of association between matrix metalloproteinases 2, 7 and 9 promoter polymorphisms and cancer risk. Mutagenesis 25:371–379

    Article  PubMed  CAS  Google Scholar 

  32. Rodriguez-Lopez J, Perez-Pampin E, Gomez-Reino JJ, Gonzalez A (2006) Regulatory polymorphisms in extracellular matrix protease genes and susceptibility to rheumatoid arthritis: a case–control study. Arthritis Res Ther 8:R1

    Article  PubMed  Google Scholar 

  33. Jacq L, Teixeira VH, Garnier S, Petit-Teixeira E, Cornelis F (2008) The MMP2 rs243865-T allele is not a major genetic factor for rheumatoid arthritis in the French Caucasian population. Int J Immunogenet 35:97–99

    Article  PubMed  CAS  Google Scholar 

  34. Hussein YM, Mohamed RH, Pasha HF, El-Shahawy EE, Alzahrani SS (2011) Association of tumor necrosis factor alpha and its receptor polymorphisms with rheumatoid arthritis in female patients. Cell Immunol 271:192–196

    Article  PubMed  CAS  Google Scholar 

  35. Yen JH, Chen CJ, Tsai WC et al (2001) Tumor necrosis factor promoter polymorphisms in patients with rheumatoid arthritis in Taiwan. J Rheumatol 28:1788–1792

    PubMed  CAS  Google Scholar 

  36. Cvetkovic JT, Wallberg-Jonsson S, Stegmayr B, Rantapaa-Dahlqvist S, Lefvert AK (2002) Susceptibility for and clinical manifestations of rheumatoid arthritis are associated with polymorphisms of the TNF-alpha, IL-1beta, and IL-1Ra genes. J Rheumatol 29:212–219

    PubMed  CAS  Google Scholar 

  37. Pawlik A, Florczak M, Ostanek L et al (2005) TNF-alpha −308 promoter polymorphism in patients with rheumatoid arthritis. Scand J Rheumatol 34:22–26

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported in part by National Natural Science Foundation of China (81371927) and Nanjing Medical University Foundation for Development of Science and Technology (06NMUZ045, 2012NJMU128).

Conflict of interest

None of the authors has any potential financial conflict of interest related to this manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ruiping Liu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sun, R., Huang, Y., Zhang, H. et al. MMP-2, TNF-α and NLRP1 polymorphisms in Chinese patients with ankylosing spondylitis and rheumatoid arthritis. Mol Biol Rep 40, 6303–6308 (2013). https://doi.org/10.1007/s11033-013-2743-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-013-2743-8

Keywords

Navigation