Skip to main content
SpringerLink
Log in

An exon polymorphism of programmed cell death 1 gene is associated with both the susceptibility and thoracolumbar kyphosis severity of ankylosing spondylitis in a Chinese Han population

  • Original Article
  • Published:
Journal of Orthopaedic Science

Abstract

Background

Although human leukocyte antigen (HLA)-B27 gene is the major susceptible gene associated with ankylosing spondylitis (AS), it has been recognized that non-HLA-B27 genes also play key roles in the development of AS. The purpose of this study is to investigate whether a single nucleotide polymorphism (SNP) in the exon region of the programmed cell death 1 (PDCD-1) gene is associated with the susceptibility or the thoracolumbar kyphosis severity of AS in a Chinese Han population.

Methods

A total of 255 AS patients between January 2008 and October 2012 were recruited in this study. Two hundred and three healthy patients were recruited as normal controls. According to the severity of thoracolumbar kyphosis, the AS patients were further divided into group A (patients with kyphosis <70°, n = 135) and group B (patients with kyphosis ≥70°, n = 120). One exon polymorphism, rs2227982 (C/T) of PDCD-1 gene, was selected for analysis. Genotyping was performed by TaqMan probe assays in all the subjects.

Results

There were significant differences of genotype distributions of rs2227982 between AS patients and normal controls. The frequency of the T allele was significantly higher in AS patients when compared with normal controls. The frequency of the T allele in group B was significantly higher than that in group A. Carriage of the TT genotype increased the risk of severe thoracolumbar kyphosis 1.9-fold in AS patients.

Conclusions

Our study confirms a significant association between the SNP rs2227982 of PDCD-1 gene and the susceptibility of AS in a Chinese Han population. Moreover, the TT genotype is suggested to be associated with the severity of thoracolumbar kyphosis secondary to AS.

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

Access this article

Log in via an institution

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

References

  1. Brown MA, Laval SH, Brophy S, Calin A. Recurrence risk modelling of the genetic susceptibility to ankylosing spondylitis. Ann Rheum Dis. 2000;59:883–6.

    Article  PubMed  CAS  Google Scholar 

  2. Brown MA, Kennedy LG, MacGregor AJ, Darke C, Duncan E, Shatford JL, Taylor A, Calin A, Wordsworth P. Susceptibility to ankylosing spondylitis in twins: the role of genes, HLA, and the environment. Arthritis Rheum. 1997;40:1823–8.

    Article  PubMed  CAS  Google Scholar 

  3. Brown MA. Genetics and the pathogenesis of ankylosing spondylitis. Curr Opin Rheumatol. 2009;21:318–23.

    Article  PubMed  CAS  Google Scholar 

  4. van der Linden SM, Valkenburg HA, de Jongh BM, Cats A. The risk of developing ankylosing spondylitis in HLA-B27 positive individuals. A comparison of relatives of spondylitis patients with the general population. Arthritis Rheum. 1984;27:241–9.

    Article  PubMed  Google Scholar 

  5. Gunal EK, Sarvan FO, Kamali S, Gul A, Inanc M, Carin M, Konice M, Aral O, Ocal L. Low frequency of HLA-B27 in ankylosing spondylitis patients from Turkey. Joint Bone Spine. 2008;75:299–302.

    Article  PubMed  Google Scholar 

  6. Azizi E, Massoud A, Amirzargar AA, Mahmoudi M, Soleimanifar N, Rezaei N, Jamshidi AR, Nikbin B, Nicknam MH. Association of CTLA4 gene polymorphism in Iranian patients with ankylosing spondylitis. J Clin Immunol. 2010;30:268–71.

    Article  PubMed  CAS  Google Scholar 

  7. Nicknam MH, Mahmoudi M, Amirzargar AA, Jamshidi AR, Rezaei N, Nikbin B. HLA-B27 subtypes and tumor necrosis factor alpha promoter region polymorphism in Iranian patients with ankylosing spondylitis. Eur Cytokine Netw. 2009;20:17–20.

    PubMed  CAS  Google Scholar 

  8. Soleimanifar N, Amirzargar AA, Mahmoudi M, Pourfathollah AA, Azizi E, Jamshidi AR, Rezaei N, Tahoori MT, Bidad K, Nikbin B, Nicknam MH. Study of programmed cell death 1 (PDCD1) gene polymorphisms in Iranian patients with ankylosing spondylitis. Inflammation. 2011;34:707–12.

    Article  PubMed  Google Scholar 

  9. James ES, Harney S, Wordsworth BP, Cookson WO, Davis SJ, Moffatt MF. PDCD1: a tissue-specific susceptibility locus for inherited inflammatory disorders. Genes Immun. 2005;6:430–7.

    Article  PubMed  CAS  Google Scholar 

  10. Nishimura H, Minato N, Nakano T, Honjo T. Immunological studies on PD-1 deficient mice: implication of PD-1 as a negative regulator for B cell responses. Int Immunol. 1998;10:1563–72.

    Article  PubMed  CAS  Google Scholar 

  11. Wang Q, Ye D, Yin J, Li X, Zhang G, Zhang Y, Zhang X. Programmed cell death 1 genotypes are associated with susceptibility to systemic lupus erythematosus among Chinese. Arch Dermatol Res. 2008;300:91–3.

    Article  PubMed  Google Scholar 

  12. Lin SC, Yen JH, Tsai JJ, Tsai WC, Ou TT, Liu HW, Chen CJ. Association of a programmed death 1 gene polymorphism with the development of rheumatoid arthritis, but not systemic lupus erythematosus. Arthritis Rheum. 2004;50:770–5.

    Article  PubMed  CAS  Google Scholar 

  13. Nielsen C, Hansen D, Husby S, Jacobsen BB, Lillevang ST. Association of a putative regulatory polymorphism in the PD-1 gene with susceptibility to type 1 diabetes. Tissue Antigens. 2003;62:492–7.

    Article  PubMed  CAS  Google Scholar 

  14. Kroner A, Mehling M, Hemmer B, Rieckmann P, Toyka KV, Maurer M, Wiendl H. A PD-1 polymorphism is associated with disease progression in multiple sclerosis. Ann Neurol. 2005;58:50–7.

    Article  PubMed  CAS  Google Scholar 

  15. Liu X, Hu LH, Li YR, Chen FH, Ning Y, Yao QF. Programmed cell death 1 gene polymorphism is associated with ankylosing spondylitis in Chinese Han population. Rheumatol Int. 2011;31:209–13.

    Article  PubMed  Google Scholar 

  16. Huang CH, Wong RH, Wei JC, Tsay MD, Chen WC, Chen HY, Shih WT, Chiou SP, Tu YC, Lee HS. Effects of genetic polymorphisms of programmed cell death 1 and its ligands on the development of ankylosing spondylitis. Rheumatology (Oxford). 2011;50:1809–13.

    Article  CAS  Google Scholar 

  17. Yang Q, Liu Y, Liu D, Zhang Y, Mu K. Association of polymorphisms in the programmed cell death 1 (PD-1) and PD-1 ligand genes with ankylosing spondylitis in a Chinese population. Clin Exp Rheumatol. 2011;29:13–8.

    PubMed  Google Scholar 

  18. Lee SH, Lee YA, Woo DH, Song R, Park EK, Ryu MH, Kim YH, Kim KS, Hong SJ, Yoo MC, Yang HI. Association of the programmed cell death 1 (PDCD1) gene polymorphism with ankylosing spondylitis in the Korean population. Arthritis Res Ther. 2006;8:R163.

    Article  PubMed  Google Scholar 

  19. Tang NL, Yeung HY, Lee KM, Hung VW, Cheung CS, Ng BK, Kwok R, Guo X, Qin L, Cheng JC. A relook into the association of the estrogen receptor [alpha] gene (PvuII, XbaI) and adolescent idiopathic scoliosis: a study of 540 Chinese cases. Spine (Phila Pa 1976). 2006;31:2463–8.

    Article  Google Scholar 

  20. Ioannidis JP, Ntzani EE, Trikalinos TA, Contopoulos-Ioannidis DG. Replication validity of genetic association studies. Nat Genet. 2001;29:306–9.

    Article  PubMed  CAS  Google Scholar 

  21. Neale BM, Sham PC. The future of association studies: gene-based analysis and replication. Am J Hum Genet. 2004;75:353–62.

    Article  PubMed  CAS  Google Scholar 

  22. Braun J, Sieper J. Ankylosing spondylitis. Lancet. 2007;369:1379–90.

    Article  PubMed  Google Scholar 

  23. van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum. 1984;27:361–8.

    Article  PubMed  Google Scholar 

  24. Qian BP, Wang XH, Qiu Y, Wang B, Zhu ZZ, Jiang J, Sun X. The influence of closing-opening wedge osteotomy on sagittal balance in thoracolumbar kyphosis secondary to ankylosing spondylitis: a comparison with closing wedge osteotomy. Spine (Phila Pa 1976). 2012;37:1415–23.

    Article  Google Scholar 

  25. Khan MA, Mathieu A, Sorrentino R, Akkoc N. The pathogenetic role of HLA-B27 and its subtypes. Autoimmun Rev. 2007;6:183–9.

    Article  PubMed  CAS  Google Scholar 

  26. Liang SC, Latchman YE, Buhlmann JE, Tomczak MF, Horwitz BH, Freeman GJ, Sharpe AH. Regulation of PD-1, PD-L1, and PD-L2 expression during normal and autoimmune responses. Eur J Immunol. 2003;33:2706–16.

    Article  PubMed  CAS  Google Scholar 

  27. Salama AD, Chitnis T, Imitola J, Ansari MJ, Akiba H, Tushima F, Azuma M, Yagita H, Sayegh MH, Khoury SJ. Critical role of the programmed death-1 (PD-1) pathway in regulation of experimental autoimmune encephalomyelitis. J Exp Med. 2003;198:71–8.

    Article  PubMed  CAS  Google Scholar 

  28. Keir ME, Liang SC, Guleria I, Latchman YE, Qipo A, Albacker LA, Koulmanda M, Freeman GJ, Sayegh MH, Sharpe AH. Tissue expression of PD-L1 mediates peripheral T cell tolerance. J Exp Med. 2006;203:883–95.

    Article  PubMed  CAS  Google Scholar 

  29. Okazaki T, Honjo T. The PD-1-PD-L pathway in immunological tolerance. Trends Immunol. 2006;27:195–201.

    Article  PubMed  CAS  Google Scholar 

  30. Nishimura H, Okazaki T, Tanaka Y, Nakatani K, Hara M, Matsumori A, Sasayama S, Mizoguchi A, Hiai H, Minato N, Honjo T. Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science. 2001;291:319–22.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors would like to acknowledge Development of Medical Technology Key Project (Nanjing, China, ZKX10008) and Medical Technology Development Project (Nanjing, China, YKK09100) for their financial supports.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Spine Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Zhongshan Road 321, Nanjing, 210008, China

    Bang-ping Qian, Xin-qiang Wang, Yong Qiu, Hua Jiang, Ming-liang Ji & Jun Jiang

Authors
  1. Bang-ping Qian
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xin-qiang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yong Qiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hua Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ming-liang Ji
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jun Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yong Qiu.

About this article

Cite this article

Qian, Bp., Wang, Xq., Qiu, Y. et al. An exon polymorphism of programmed cell death 1 gene is associated with both the susceptibility and thoracolumbar kyphosis severity of ankylosing spondylitis in a Chinese Han population. J Orthop Sci 18, 514–518 (2013). https://doi.org/10.1007/s00776-013-0385-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00776-013-0385-2

Keywords

Search

Navigation