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Apoptosis-related Fas and FasL gene polymorphisms’ associations with knee osteoarthritis

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Abstract

To investigate the associations between Fas and FasL gene polymorphisms and susceptibility to knee osteoarthritis. Genomic DNA was obtained from 146 patients with knee osteoarthritis and 102 healthy controls. Genotype distributions and allelic frequencies of four polymorphisms of Fas (-670 G>A rs1800682, -1377 G>A rs2234767) and FasL (IVS2nt-124 A>G rs5030772, -844 T>C rs763110) genes were compared between the groups. Thereafter, this association was investigated between patients and controls of the same sex. There were significant differences between patients with knee osteoarthritis and controls regarding the genotype distributions and allelic frequencies of Fas-1377 G>A polymorphism (P = 0.0001 and P = 0.005, respectively). The Fas-1377 GG genotype and G allele were significantly more frequent in patients with knee osteoarthritis than in controls. Genotype distributions and allelic frequencies of Fas-670 G>A, FasL-844 T>C, and FasL IVS2nt-124 A>G polymorphisms did not differ between the groups (P > 0.05). However, there were no significant differences between patients and controls of the same sex (P > 0.05). These findings suggest that the Fas-1377 G>A polymorphism in the Fas gene related with apoptosis may contribute to susceptibility to knee osteoarthritis in the Turkish population. There is a need for further studies to evaluate the role of apoptosis in large cohorts.

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References

  1. Hamerman D (1993) Aging and osteoarthritis: basic mechanisms. J Am Geriatr Soc 41:760–770

    PubMed  CAS  Google Scholar 

  2. Westacott CI, Sharif M (1996) Cytokines in osteoarthritis: mediators or markers of joint destruction? Semin Arthritis Rheum 25:254–272

    Article  PubMed  CAS  Google Scholar 

  3. Goldring MB (2000) The role of the chondrocyte in osteoarthritis. Arthritis Rheum 43:1916–1926

    Article  PubMed  CAS  Google Scholar 

  4. Sharif M, Whitehouse A, Sharman P, Perry M, Adams M (2004) Increased apoptosis in human osteoarthritic cartilage corresponds to reduced cell density and expression of caspase-3. Arthritis Rheum 50:507–515

    Article  PubMed  CAS  Google Scholar 

  5. Aigner T, Kim HA (2002) Apoptosis and cellular vitality: issues in osteoarthritic cartilage degradation. Arthritis Rheum 46:1986–1996

    Article  PubMed  CAS  Google Scholar 

  6. Goggs R, Carter SD, Schulze-Tanzil G, Shakibaei M, Mobasheri A (2002) Apoptosis and the loss of chondrocyte survival signals contribute to articular cartilage degradation in osteoarthritis. Vet J 166:140–158

    Article  Google Scholar 

  7. Lotz M, Hashimoto S, Kuhn K (1999) Mechanisms of chondrocyte apoptosis. Osteoarthr Cartil 7:389–391

    Article  PubMed  CAS  Google Scholar 

  8. Mobasheri A (2002) Role of chondrocyte death and hypocellularity in aging human articular cartilage and the pathogenesis of osteoarthritis. Med Hypotheses 58:193–197

    Article  PubMed  CAS  Google Scholar 

  9. Blanco FJ, Guitian R, Vazquez-Martul E, de Toro FJ, Galdo F (1998) Osteoarthritis chondrocytes die by apoptosis: a possible pathway for osteoarthritis pathology. Arthritis Rheum 41:284–289

    Article  PubMed  CAS  Google Scholar 

  10. Heraud F, Heraud A, Harmand MF (2000) Apoptosis in normal and osteoarthritic human articular cartilage. Ann Rheum Dis 59:959–965

    Article  PubMed  CAS  Google Scholar 

  11. Kim HA, Suh DI, Song YW (2001) Relationship between chondrocyte apoptosis and matrix depletion in human articular cartilage. J Rheumatol 28:2038–2045

    PubMed  CAS  Google Scholar 

  12. Pennock AT, Robertson CM, Emmerson BC, Harwood FL, Amiel D (2007) Role of apoptotic and matrix-degrading genes in articular cartilage and meniscus of mature and aged rabbits during development of osteoarthritis. Arthritis Rheum 56:1529–1536

    Article  PubMed  Google Scholar 

  13. Alenzi FQ (2005) Apoptosis and diseases: regulation and clinical relevance. Saudi Med J 26:1679–1690

    PubMed  Google Scholar 

  14. D’Lima DD, Hashimoto S, Chen PC, Lotz MK, Colwell CW Jr (2001) Prevention of chondrocyte apoptosis. J Bone Joint Surg Am 83:25–26

    PubMed  Google Scholar 

  15. Kim HA, Lee YJ, Seong SC, Choe KW, Song YW (2000) Apoptotic chondrocyte death in human osteoarthritis. J Rheumatol 27:455–462

    PubMed  CAS  Google Scholar 

  16. Musumeci G, Loreto C, Carnazza ML, Martinez G (2011) Characterization of apoptosis in articular cartilage derived from the knee joints of patients with osteoarthritis. Knee Surg Sports Traumatol Arthrosc 192:307–313

    Article  Google Scholar 

  17. Itoh N, Yonehara S, Ishii A et al (1991) The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell 66:233–243

    Article  PubMed  CAS  Google Scholar 

  18. Oehm A, Behrmann I, Falk W et al (1992) Purification and molecular cloning of the APO-1 cell surface antigen, a member of the tumor necrosis factor/nerve growth factor receptor superfamily. sequence identity with the Fas antigen. J Biol Chem 267:10709–10715

    PubMed  CAS  Google Scholar 

  19. Huang QR, Morris D, Manolios N (1997) Identification and characterization of polymorphisms in the promoter region of the human Apo-1/Fas (CD95) gene. Mol Immunol 34:577–582

    Article  PubMed  CAS  Google Scholar 

  20. Sibley K, Rollinson S, Allan JM et al (2003) Functional FAS promoter polymorphisms are associated with increased risk of acute myeloid leukemia. Cancer Res 63:4327–4330

    PubMed  CAS  Google Scholar 

  21. Wu J, Metz C, Xu X, Abe R, Gibson AW, Edberg JC (2003) A novel polymorphic CAAT/enhancer-binding protein beta element in the FasL gene promoter alters Fas ligand expression: a candidate background gene in African American systemic lupus erythematosus patients. J Immunol 70:132–138

    Google Scholar 

  22. Cohen PL, Eisenberg RA (1991) Lpr and gld: single gene models of systemic autoimmunity and lymphoproliferative disease. Annu Rev Immunol 9:243–269

    Article  PubMed  CAS  Google Scholar 

  23. Das H, Koizumi T, Sugimoto T, Chakraborty S, Ichimura T, Hasegawa K, Nishimura R (2000) Quantitation of Fas and Fas ligand gene expression in human ovarian, cervical and endometrial carcinomas using real-time quantitative RT-PCR. Br J Cancer 82:1682–1688

    Article  PubMed  CAS  Google Scholar 

  24. Mohammadzadeh A, Pourfathollah AA, Tahoori MT, Daneshmandi S, Langroudi L, Akhlaghi M (2011) Evaluation of apoptosis-related gene Fas (CD95) and FasL (CD178) polymorphisms in Iranian rheumatoid arthritis patients. Rheumatol Int 31. doi:10.1007/s00296-011-2065-x

  25. Wang LE, Cheng L, Spitz MR, Wei Q (2003) Fas A670G polymorphism, apoptotic capacity in lymphocyte cultures, and risk of lung cancer. Lung Cancer 42:1–8

    Article  PubMed  CAS  Google Scholar 

  26. Lai HC, Sytwu HK, Sun CA et al (2003) Single nucleotide polymorphism at Fas promoter is associated with cervical carcinogenesis. Int J Cancer 103:221–225

    Article  PubMed  CAS  Google Scholar 

  27. Zhu J, Qin C, Wang M et al (2010) Functional polymorphisms in cell death pathway genes and risk of renal cell carcinoma. Mol Carcinog 49:810–817

    PubMed  CAS  Google Scholar 

  28. Li C, WuW Liu J et al (2006) Functional polymorphisms in the promoter regions of the FAS and FAS ligand genes and risk of bladder cancer in south China: a case–control analysis. Pharmacogenet Genomics 16:245–251

    Article  PubMed  CAS  Google Scholar 

  29. Sun T, Miao X, Zhang X, Tan W, Xiong P, Lin D (2004) Polymorphisms of death pathway genes FAS and FASL in esophageal squamous cell carcinoma. J Natl Cancer Inst 96:1030–1036

    Article  PubMed  CAS  Google Scholar 

  30. Chen JY, Wang CM, Ma CC, Chow YH, Luo SF (2005) The _844C/T polymorphism in the Fas ligand promoter associates with Taiwanese SLE. Genes Immun 6:123–128

    Article  PubMed  CAS  Google Scholar 

  31. Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16(3):1215

    Article  PubMed  CAS  Google Scholar 

  32. Fuks A, Parton LA, Polavarapu S, Netta D, Strassberg S, Godi I, Hsu CD (2005) Polymorphism of Fas and Fas ligand in preterm premature rupture of membranes in singleton pregnancies. Am J Obstet Gynecol 193:1132–1136

    Article  PubMed  CAS  Google Scholar 

  33. Aguilar-Reina J, Ruiz-Ferrer M, Pizarro MA, Antiñolo G (2005) The-670A>G polymorphism in the promoter region of the FAS gene is associated with necrosis in periportal areas in patients with chronic hepatitis C. J Viral Hepat 12:568–573

    Article  PubMed  CAS  Google Scholar 

  34. Li C, Larson D, Zhang Z et al (2006) Polymorphisms of the FAS and FAS ligand genes associated with risk of cutaneous malignant melanoma. Pharmacogenet Genomics 16:253–263

    Article  PubMed  Google Scholar 

  35. Zhang X, Miao X, Sun T, Tan W, Qu S, Xiong P, Zhou Y, Lin D (2005) Functional polymorphisms in cell death pathway genes FAS and FASL contribute to risk of lung cancer. J Med Genet 42:479–484

    Article  PubMed  CAS  Google Scholar 

  36. Stuck BJ, Pani MA, Besrour F, Segni M, Krause M, Usadel KH, Badenhoop K (2003) Fas ligand gene polymorphisms are not associated with Hashimoto’s thyroiditis and Graves’ disease. Hum Immunol 64:285–289

    Article  PubMed  CAS  Google Scholar 

  37. Hashimoto S, Setareh M, Ochs RL, Lotz M (1997) Fas/Fas ligand expression and induction of apoptosis in chondrocytes. Arthritis Rheum 40:1749–1755

    Article  PubMed  CAS  Google Scholar 

  38. Robertson CM, Pennock AT, Harwood FL, Pomerleau AC, Allen RT, Amiel D (2006) Characterization of pro-apoptotic and matrix-degradative gene expression following induction of osteoarthritis in mature and aged rabbits. Osteoarthritis Cartilage 14:471–476

    Article  PubMed  CAS  Google Scholar 

  39. Kanemitsu S, Ihara K, Saifddin A, Otsuka T, Takeuchi T, Nagayama J (2002) A functional polymorphism in fas (CD95/APO-1) gene promoter associated with systemic lupus erythematosus. J Rheumatol 29:1183–1188

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This was not an industry-supported study. All authors have reported no financial conflicts of interest. There was no investigational or off-label use.

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Correspondence to Melek Sezgin.

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Sezgin, M., Barlas, İ.Ö., Yıldır, S. et al. Apoptosis-related Fas and FasL gene polymorphisms’ associations with knee osteoarthritis. Rheumatol Int 33, 2039–2043 (2013). https://doi.org/10.1007/s00296-013-2688-1

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  • DOI: https://doi.org/10.1007/s00296-013-2688-1

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