Skip to main content

Advertisement

Log in

Association of polymorphisms in TNF and GRN genes with ankylosing spondylitis in a Chinese Han population

  • Genes and Disease
  • Published:
Rheumatology International Aims and scope Submit manuscript

Abstract

The aim of this study is to investigate the association of the polymorphisms in tumor necrosis factor (TNF) and granulin (GRN) with ankylosing spondylitis (AS) in a Chinese Han population. Five single nucleotide polymorphisms (SNPs) covering TNF and six SNPs covering GRN were investigated in 861 Chinese Han AS patients and 864 healthy controls. For rs1799964, the C allele was linked to reduced risk of AS (p < 0.0001, OR = 0.60, 95% CI = 0.50–0.71). The carriers of the C/C homozygote showed a significantly lower risk of AS compared with the TT homozygote and the C/T heterozygote under the recessive model (p < 0.0001, OR = 0.23, 95% CI = 0.12–0.45). For rs1800629, the A allele was also linked to reduced risk of AS (p < 0.0001, OR = 0.54, 95% CI = 0.39–0.74). For rs1800630, the A allele was also linked to reduced risk of AS (p < 0.0001, OR = 0.59, 95% CI = 0.48–0.72). The carriers of the A/A homozygote showed a significantly lower risk of AS compared with the C/C homozygote and the A/C heterozygote under the recessive model (p < 0.0001, OR = 0.18, 95% CI = 0.07–0.47). For rs769178, the T allele was linked to increased risk of AS (p < 0.0001, OR = 2.59, 95% CI = 2.18–3.09). The carriers of the T/T homozygote showed a significantly higher risk of AS compared with the GG homozygote and the G/T heterozygote under the recessive model (p < 0.0001, OR = 3.34, 95 %CI = 1.95–5.72). There was no significant difference between the AS patients and the controls in the genotype or allele frequencies of rs361525. For GRN, there was no significant difference between the AS patients and the controls in the genotype or allele frequencies of rs25646, rs3760365, rs3785817, rs4792939, rs5848, rs850713 (p > 0.05). This study indicates that polymorphisms in TNF are related to AS, but polymorphisms in GRN are not related to AS susceptibility in a Chinese Han population.

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.

Similar content being viewed by others

References

  1. Liu CJ, Bosch X (2012) Progranulin: a growth factor, a novel TNFR ligand and a drug target. Pharmacol Ther 133(1):124–132

    Article  CAS  PubMed  Google Scholar 

  2. Thurner L, Preuss KD, Fadle N, Regitz E, Klemm P, Zaks M et al (2013) Progranulin antibodies in autoimmune diseases. J Autoimmun 42:29–38

    Article  CAS  PubMed  Google Scholar 

  3. Machado MA, Barbosa MM, Almeida AM, de Araújo VE, Kakehasi AM, Andrade EI et al (2013) Treatment of ankylosing spondylitis with TNF blockers: a meta-analysis. Rheumatol Int 33(9):2199–2213

    Article  CAS  PubMed  Google Scholar 

  4. Zhu X, Wang Y, Sun L, Song Y, Sun F, Tang L, Huo Z, Li J, Yang Z (2007) A novel gene variation of TNF alpha associated with ankylosing spondylitis: a reconfirmed study. Ann Rheum Dis 66(11):1419–1422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Nossent JC, Sagen-Johnsen S, Bakland G (2014) Tumor necrosis factor-α promoter -308/238 polymorphism association with less severe disease in ankylosing spondylitis is unrelated to serum TNF-α and does not predict TNF inhibitor response. J Rheumatol 41(8):1675–1682

    Article  CAS  PubMed  Google Scholar 

  6. Jia Y, Qin HJ, Zhang JX, Liu XL, Li LJ (2013) Association of the tumour necrosis factor-α polymorphisms rs361525 and rs1800629 with susceptibility to psoriasis: a meta-analysis. Clin Exp Dermatol 38(8):836–844

    Article  CAS  PubMed  Google Scholar 

  7. Tong Q, Zhao DB, Bajracharya P et al (2012) TNF-α-857 and -1031 polymorphisms predict good therapeutic response to TNF-α blockers in Chinese Han patients with ankylosing spondylitis. Pharmacogenomics 13(13):1459–1467

    Article  CAS  PubMed  Google Scholar 

  8. Thurner L, Zaks M, Preuss KD, Fadle N, Regitz E, Ong MF et al (2013) Progranulin antibodies entertain a proinflammatory environment in a subgroup of patients with psoriatic arthritis. Arthritis Res Ther 15(6):R211

    Article  PubMed  PubMed Central  Google Scholar 

  9. 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. Arthr Rheum 27(4):361–368

    Article  Google Scholar 

  10. Shi YY, He L (2005) SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci. Cell Res 15(2):97–98

    Article  CAS  PubMed  Google Scholar 

  11. Braun J et al (1995) Use of immunohistologic and in situ hybridization techniques in the examination of sacroiliac joint biopsy specimens from patients with ankylosing spondylitis. Arthritis Rheum 38:499–505

    Article  CAS  PubMed  Google Scholar 

  12. McLeod C et al (2007) Adalimumab, etanercept and infliximab for the treatment of ankylosing spondylitis: a systematic review and economic evaluation. Health Technol Assess 11(28):1–158, iii–iv

    Article  CAS  Google Scholar 

  13. Callhoff J, Sieper J, Weiß A, Zink A, Listing J (2015) Efficacy of TNFα blockers in patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis: a meta-analysis. Ann Rheum Dis 74(6):1241–1248

    Article  CAS  PubMed  Google Scholar 

  14. Robinson PC, Brown MA (2014) Genetics of ankylosing spondylitis. Mol Immunol 57(1):2–11

  15. Ji Y, Yang X, Yang L, Wu D, Hua F, Lu T et al (2013) Studies on correlation between single-nucleotide polymorphisms of tumor necrosis factor gene and different stages of ankylosing spondylitis. Cell Biochem Biophys 67(3):915–922

    Article  CAS  PubMed  Google Scholar 

  16. Toonen EJ, Barrera P, Fransen J, de Brouwer AP, Eijsbouts AM, Miossec P et al (2012) Meta-analysis identified the TNFA -308G > A promoter polymorphism as a risk factor for disease severity in patients with rheumatoid arthritis. Arthritis Res Ther 14(6):R264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Sun R, Huang Y, Zhang H, Liu R (2013) MMP-2, TNF-α and NLRP1 polymorphisms in Chinese patients with ankylosing spondylitis and rheumatoid arthritis. Mol Biol Rep 40(11):6303–6308

    Article  CAS  PubMed  Google Scholar 

  18. Radouane A, Oudghiri M, Chakib A, Bennani S, Touitou I, Barat-Houari M (2012) SNPs in the TNF-α gene promoter associated with Behcet’s disease in Moroccan patients. Rheumatology 51(9):1595–1599

    Article  CAS  PubMed  Google Scholar 

  19. Tang W, Lu Y, Tian QY, Zhang Y, Guo FJ, Liu GY et al (2011) The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice. Science 332(6028):478–484

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by Foundation of Primary Research & Development Plan of Shandong Province (2015GSF118002). In the later time, we also received support from Natural Science Foundation of China Grant (81671605).

Author information

Authors and Affiliations

Authors

Contributions

Q. Yang and Y. Cui conceived and designed the study. N. Hu, X. Yang and L. Wang performed the experiments. H. Xu provided the experiment. N. Hu wrote the paper. Q. Yang and H. Xu reviewed and edited the manuscript. All authors read and approved the manuscript.

Corresponding author

Correspondence to Qingrui Yang.

Ethics declarations

Research involving human participants and/or animals

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.

Informed consent

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

Conflict of interest

All authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hu, N., Cui, Y., Yang, Q. et al. Association of polymorphisms in TNF and GRN genes with ankylosing spondylitis in a Chinese Han population. Rheumatol Int 38, 481–487 (2018). https://doi.org/10.1007/s00296-017-3899-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-017-3899-7

Keywords

Navigation