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.
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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
Braun J, Sieper J (2007) Ankylosing spondylitis. Lancet 369:1379–1390
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
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
Parks WC, Wilson CL, Lopez-Boado YS (2004) Matrix metalloproteinases as modulators of inflammation and innate immunity. Nat Rev Immunol 4:617–629
Huang H, Zhao W, Tang Z et al (2009) Characterization of porcine MMP-2 and its association with immune traits. Gene 435:63–71
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Jin Y, Mailloux CM, Gowan K et al (2007) NALP1 in vitiligo-associated multiple autoimmune disease. N Engl J Med 356:1216–1225
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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).
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None of the authors has any potential financial conflict of interest related to this manuscript.
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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
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DOI: https://doi.org/10.1007/s11033-013-2743-8