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Fas/FasL, Bcl2 and Caspase-8 gene polymorphisms in Chinese patients with rheumatoid arthritis

  • Genes and Disease
  • Published:
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Abstract

Apoptosis signals are necessary for maintaining homeostasis and an adequate immune response. Dysregulation of apoptosis-related genes in the immune system has an important impact on autoimmune diseases such as rheumatoid arthritis (RA). Thus, we investigated the association between Fas rs2234767 G/A, FasL rs763110 C/T, Bcl2 rs12454712 T/C, Bcl2 rs17757541 C/G, and Caspase-8 rs1035142 G/T polymorphisms and RA susceptibility in a Chinese population. These five single-nucleotide polymorphisms (SNPs) were studied in a Chinese population consisting of 615 patients with RA and 839 controls. Genotyping was performed using a custom-by-design 48-Plex SNP scan TM kit. Furthermore, we undertook a meta-analysis between FasL rs763110 C/T and RA. This study indicated that Fas rs2234767 and Bcl2 rs17757541 polymorphisms were risk factors for RA. No association was observed between FasL rs763110 C/T, Bcl2 rs12454712 T/C, and Caspase-8 rs1035142 G/T polymorphisms and RA in this study. The results of this meta-analysis suggested no significant association between FasL rs763110 C/T and RA. However, stratification analysis of this meta-analysis indicated that FasL rs763110 C/T increased the risk of Caucasian RA patients. In conclusion, this study demonstrated that Fas rs2234767 G/A and Bcl2 rs17757541 T/C polymorphisms might be associated with an increased risk of RA. This meta-analysis revealed that FasL rs763110 C/T was associated with an increased risk of Caucasian RA patients.

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Abbreviations

CI:

Confidence interval

RA:

Rheumatoid arthritis

OR:

Odds ratio

SNP:

Single-nucleotide polymorphism

Bcl2:

B-cell lymphoma 2

References

  1. Kalinina Ayuso V, Makhotkina N, van Tent-Hoeve M, de Groot-Mijnes JD, Wulffraat NM, Rothova A, de Boer JH (2014) Pathogenesis of juvenile idiopathic arthritis associated uveitis: the known and unknown. Surv Ophthalmol 59(5):517–531. doi:10.1016/j.survophthal.2014.03.002

    Article  PubMed  Google Scholar 

  2. Silman AJ (1997) Problems complicating the genetic epidemiology of rheumatoid arthritis. J Rheumatol 24(1):194–196

    CAS  PubMed  Google Scholar 

  3. Taneja V, Giphart MJ, Verduijn W, Naipal A, Malaviya AN, Mehra NK (1996) Polymorphism of HLA-DRB, -DQA1, and -DQB1 in rheumatoid arthritis in Asian Indians: association with DRB1*0405 and DRB1*1001. Hum Immunol 46(1):35–41

    Article  CAS  PubMed  Google Scholar 

  4. Hasunuma T, Kayagaki N, Asahara H, Motokawa S, Kobata T, Yagita H, Aono H, Sumida T, Okumura K, Nishioka K (1997) Accumulation of soluble Fas in inflamed joints of patients with rheumatoid arthritis. Arthritis Rheum 40(1):80–86

    Article  CAS  PubMed  Google Scholar 

  5. Pope RM (2002) Apoptosis as a therapeutic tool in rheumatoid arthritis. Nat Rev Immunol 2(7):527–535. doi:10.1038/nri846

    Article  CAS  PubMed  Google Scholar 

  6. Itoh N, Yonehara S, Ishii A, Yonehara M, Mizushima S, Sameshima M, Hase A, Seto Y, Nagata S (1991) The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell 66(2):233–243

    Article  CAS  PubMed  Google Scholar 

  7. Krammer PH, Behrmann I, Daniel P, Dhein J, Debatin KM (1994) Regulation of apoptosis in the immune system. Curr Opin Immunol 6(2):279–289

    Article  CAS  PubMed  Google Scholar 

  8. Asahara H, Hasunuma T, Kobata T, Inoue H, Muller-Ladner U, Gay S, Sumida T, Nishioka K (1997) In situ expression of protooncogenes and Fas/Fas ligand in rheumatoid arthritis synovium. J Rheumatol 24(3):430–435

    CAS  PubMed  Google Scholar 

  9. Schulte M, Reiss K, Lettau M, Maretzky T, Ludwig A, Hartmann D, de Strooper B, Janssen O, Saftig P (2007) ADAM10 regulates FasL cell surface expression and modulates FasL-induced cytotoxicity and activation-induced cell death. Cell Death Differ 14(5):1040–1049. doi:10.1038/sj.cdd.4402101

    CAS  PubMed  Google Scholar 

  10. Calmon-Hamaty F, Audo R, Combe B, Morel J, Hahne M (2015) Targeting the Fas/FasL system in rheumatoid arthritis therapy: promising or risky? Cytokine 75(2):228–233. doi:10.1016/j.cyto.2014.10.004

    Article  CAS  PubMed  Google Scholar 

  11. Watanabe-Fukunaga R, Brannan CI, Copeland NG, Jenkins NA, Nagata S (1992) Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature 356(6367):314–317. doi:10.1038/356314a0

    Article  CAS  PubMed  Google Scholar 

  12. Mohammadzadeh A, Pourfathollah AA, Tahoori MT, Daneshmandi S, Langroudi L, Akhlaghi M (2012) Evaluation of apoptosis-related gene Fas (CD95) and FasL (CD178) polymorphisms in Iranian rheumatoid arthritis patients. Rheumatol Int 32(9):2833–2836. doi:10.1007/s00296-011-2065-x

    Article  CAS  PubMed  Google Scholar 

  13. Yildir S, Sezgin M, Barlas IO, Turkoz G, Ankarali HC, Sahin G, Erdal ME (2013) Relation of the Fas and FasL gene polymorphisms with susceptibility to and severity of rheumatoid arthritis. Rheumatol Int 33(10):2637–2645. doi:10.1007/s00296-013-2793-1

    Article  CAS  PubMed  Google Scholar 

  14. Byun HS, Song JK, Kim YR, Piao L, Won M, Park KA, Choi BL, Lee H, Hong JH, Park J, Seok JH, Lee YJ, Kang SW, Hur GM (2008) Caspase-8 has an essential role in resveratrol-induced apoptosis of rheumatoid fibroblast-like synoviocytes. Rheumatology 47(3):301–308. doi:10.1093/rheumatology/kem368

    Article  CAS  PubMed  Google Scholar 

  15. Palao G, Santiago B, Galindo MA, Rullas JN, Alcami J, Ramirez JC, Pablos JL (2006) Fas activation of a proinflammatory program in rheumatoid synoviocytes and its regulation by FLIP and caspase 8 signaling. Arthritis Rheum 54(5):1473–1481. doi:10.1002/art.21768

    Article  CAS  PubMed  Google Scholar 

  16. Kammouni W, Wong K, Ma G, Firestein GS, Gibson SB, El-Gabalawy HS (2007) Regulation of apoptosis in fibroblast-like synoviocytes by the hypoxia-induced Bcl-2 family member Bcl-2/adenovirus E1B 19-kd protein-interacting protein 3. Arthritis Rheum 56(9):2854–2863. doi:10.1002/art.22853

    Article  CAS  PubMed  Google Scholar 

  17. Kobak S, Berdeli A (2012) Fas/FasL promoter gene polymorphism in patients with rheumatoid arthritis. Reumatismo 64(6):374–379. doi:10.4081/reumatismo.2012.374

    Article  CAS  PubMed  Google Scholar 

  18. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31(3):315–324

    Article  CAS  PubMed  Google Scholar 

  19. Zheng L, Yin J, Wang L, Wang X, Shi Y, Shao A, Tang W, Ding G, Liu C, Chen S, Gu H (2013) Interleukin 1B rs16944 G> A polymorphism was associated with a decreased risk of esophageal cancer in a Chinese population. Clin Biochem 46(15):1469–1473. doi:10.1016/j.clinbiochem.2013.05.050

    Article  CAS  PubMed  Google Scholar 

  20. Stang A (2010) Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25(9):603–605. doi:10.1007/s10654-010-9491-z

    Article  PubMed  Google Scholar 

  21. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558. doi:10.1002/sim.1186

    Article  PubMed  Google Scholar 

  22. Okamoto K, Asahara H, Kobayashi T, Matsuno H, Hasunuma T, Kobata T, Sumida T, Nishioka K (1998) Induction of apoptosis in the rheumatoid synovium by Fas ligand gene transfer. Gene Ther 5(3):331–338. doi:10.1038/sj.gt.3300597

    Article  CAS  PubMed  Google Scholar 

  23. Pundt N, Peters MA, Wunrau C, Strietholt S, Fehrmann C, Neugebauer K, Seyfert C, van Valen F, Pap T, Meinecke I (2009) Susceptibility of rheumatoid arthritis synovial fibroblasts to FasL- and TRAIL-induced apoptosis is cell cycle-dependent. Arthritis Res Ther 11(1):R16. doi:10.1186/ar2607

    Article  PubMed  PubMed Central  Google Scholar 

  24. Okamoto K, Kobayashi T, Kobata T, Hasunuma T, Kato T, Sumida T, Nishioka K (2000) Fas-associated death domain protein is a Fas-mediated apoptosis modulator in synoviocytes. Rheumatology 39(5):471–480

    Article  CAS  PubMed  Google Scholar 

  25. Nakajima T, Aono H, Hasunuma T, Yamamoto K, Shirai T, Hirohata K, Nishioka K (1995) Apoptosis and functional Fas antigen in rheumatoid arthritis synoviocytes. Arthritis Rheum 38(4):485–491

    Article  CAS  PubMed  Google Scholar 

  26. Asahara H, Hasumuna T, Kobata T, Yagita H, Okumura K, Inoue H, Gay S, Sumida T, Nishioka K (1996) Expression of Fas antigen and Fas ligand in the rheumatoid synovial tissue. Clin Immunol Immunopathol 81(1):27–34

    Article  CAS  PubMed  Google Scholar 

  27. Firestein GS, Yeo M, Zvaifler NJ (1995) Apoptosis in rheumatoid arthritis synovium. J Clin Investig 96(3):1631–1638. doi:10.1172/JCI118202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Cohen PL, Eisenberg RA (1991) Lpr and gld: single gene models of systemic autoimmunity and lymphoproliferative disease. Annu Rev Immunol 9:243–269. doi:10.1146/annurev.iy.09.040191.001331

    Article  CAS  PubMed  Google Scholar 

  29. 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(10):1682–1688. doi:10.1054/bjoc.2000.1118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Lee YH, Bae SC, Song GG (2015) Association between the CTLA-4, CD226, FAS polymorphisms and rheumatoid arthritis susceptibility: a meta-analysis. Hum Immunol 76(2–3):83–89. doi:10.1016/j.humimm.2015.01.023

    Article  CAS  PubMed  Google Scholar 

  31. Lee YH, Bae SC, Choi SJ, Ji JD, Song GG (2012) Associations between the FAS −670 A/G and −1,377 G/A polymorphisms and susceptibility to autoimmune rheumatic diseases: a meta-analysis. Mol Biol Rep 39(12):10671–10679. doi:10.1007/s11033-012-1957-5

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study was supported in part by National Natural Science Foundation of China (81371927).

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Author notes

    Authors and Affiliations

    1. Department of Orthopaedics, The Jintan Hospital Affiliated to Jiangsu University, Changzhou, 213200, China

      Aiping Zhu

    2. Department of Orthopedic Trauma, Affiliated Hospital of Nanjing Medical University, Changzhou Second People’s Hospital, Changzhou, 213003, China

      Mingjie Wang, Guoxin Zhou, Hui Zhang & Ruiping Liu

    3. Central Laboratory, Affiliated Hospital of Nanjing Medical University, Changzhou Second People’s Hospital, Changzhou, 213003, China

      Ruiping Liu & Yong Wang

    4. Department of Cardiothoracic Surgery, Affiliated Hospital of Nanjing Medical University, Changzhou Second People’s Hospital, Changzhou, 213003, China

      Yong Wang

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    1. Aiping Zhu
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    Correspondence to Ruiping Liu or Yong Wang.

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    All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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    Informed consent was obtained from all individual participants included in the study.

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    Aiping Zhu and Mingjie Wang have contributed equally to this study.

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    Zhu, A., Wang, M., Zhou, G. et al. Fas/FasL, Bcl2 and Caspase-8 gene polymorphisms in Chinese patients with rheumatoid arthritis. Rheumatol Int 36, 807–818 (2016). https://doi.org/10.1007/s00296-016-3443-1

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    • DOI: https://doi.org/10.1007/s00296-016-3443-1

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