Skip to main content

Advertisement

Log in

Genetic variant of IL-10RA and susceptibility to rheumatoid arthritis in a Chinese population

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

The aim of this study was to investigate the relationship between the single-nucleotide polymorphisms (SNPs) of interleukin 10 alpha receptor (IL10RA) gene and rheumatoid arthritis (RA) in a Chinese population. We examined 533 RA patients and 958 subjects as a control group. Three IL-10RA SNPs (rs9610, rs2229113 and rs3135932) were genotyped using TaqMan genotyping assays on Fluidigm 192.24 system. The IL-10RA rs9610 A allele was increased in patient group compared with control subjects (OR = 1.232, 95 % CI = 1.052–1.442, p = 0.030). Significant difference in genotype distribution was found in RA patients and controls (χ2 = 15.32, p < 0.001). We also discovered a statistical significance under the dominant model (GG + AG versus AA: OR = 0.676, 95 % CI = 0.546–0.837, p < 0.001). However, no significant difference was discovered in the recessive model (GG versus AG + AA: OR = 1.013, 95 % CI = 0.754–1.361, p = 0.932). Interestingly, significant differences were detected both in the allele and genotype frequencies of rs9610 between anti-CCP positive patients and anti-CCP negative patients (χ2 = 7.209, p = 0.007; χ2 = 9.061, p = 0.011; respectively). We also found a significant difference in genotype frequency at rs9610 in females compared with males (χ2 = 7.658, p = 0.022). Unfortunately, we failed to find any significant results between two IL-10RA SNPs (rs2229113 and rs3135932) and RA susceptibility. The findings suggest that IL-10RA rs9610 polymorphism might contribute to RA susceptibility.

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. McInnes IB, Schett G (2011) The pathogenesis of rheumatoid arthritis. N Engl J Med 365(23):2205–2019

    Article  CAS  PubMed  Google Scholar 

  2. Silman AJ, and Hochberg MC (1993) Epidemiology of the rheumatic diseases. Oxford University Press, New York 504:31–71

  3. AJ M, Snieder H, AS R, Koskenvuo M, Kaprio J, Aho K, AJ S (2000) Characterizing the quantitative genetic contribution to rheumatoid arthritis using data from twins. Arthritis Rheum 43(1):30–37

    Article  Google Scholar 

  4. de Vries R (2011) Genetics of rheumatoid arthritis: time for a change! Curr Opin Rheumatol 23(3):227–232

    Article  PubMed  Google Scholar 

  5. Deighton CM, Walker DJ, Griffiths ID, Roberts DF (1989) The contribution of HLA to rheumatoid arthritis. Clin Genet 36:178–182

    Article  CAS  PubMed  Google Scholar 

  6. Kremer JM et al (2003) Treatment of rheumatoid arthritis by selective inhibition of T-cell activation with fusion protein CTLA4Ig. N Engl JMed 349(20):1907–1915

    Article  CAS  Google Scholar 

  7. Edwards JC, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P, Close DR et al (2004) Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med 350(25):2572–2581

    Article  CAS  PubMed  Google Scholar 

  8. Peng H, Wang W, Zhou M, Li R, Pan HF, Ye DQ (2013) Role of interleukin-10 and interleukin-10 receptor in systemic lupus erythematosus. Clin Rheumatol 32(9):1255–1266

    Article  PubMed  Google Scholar 

  9. Llorente L, Richaud-Patin Y, Fior R, Alcocer-Varela J, Wijdenes J, Fourrier BM et al (1994) In vivo production of interleukin-10 by non-T cells in rheumatoid arthritis, Sjogren’s syndrome, and systemic lupus erythematosus. A potential mechanism of B lymphocyte hyperactivity and autoimmunity. Arthritis Rheum 37:1647–1655

    Article  CAS  PubMed  Google Scholar 

  10. Kirkham BW, MN L, JP E, KM J, PA B, CS L et al (2006) Synovial membrane cytokine expression is predictive of joint damage progression in rheumatoid arthritis. Arthritis Rheum 54:1122–1131

    Article  CAS  PubMed  Google Scholar 

  11. SP S, Thumboo J, Vasoo S, ST T, Tse C, KY F (2007) In vivo pro and anti-inflammatory cytokines in normal and patients with rheumatoid arthritis. Ann Acad Med Singap 36:96–99

    Google Scholar 

  12. Moore KW, de Waal MR, Coffman RL, O’Garra A (2001) Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 19:683–765

    Article  CAS  PubMed  Google Scholar 

  13. Taga K, Tosato G (1992) IL-10 inhibits human T cell proliferation and IL-2 production. J Immunol 148:1143–1148

    CAS  PubMed  Google Scholar 

  14. JD W, EL L, CA C, Weiss K, Kovesdi I, JC G et al (1999) Adenoviral transfer of the viral IL-10 gene periarticularly to mouse paws suppresses development of collagen-induced arthritis in both injected and uninjected paws. J Immunol 162:3625–3632

    Google Scholar 

  15. RP D, Dickensheets H, DS F (1999) The interleukin-10 signal transduction pathway and regulation of gene expression in mononuclear phagocytes. J Interf Cytokine Res 19(6):563–573

    Article  Google Scholar 

  16. Kotenko SV, Pestka S (2000) Jak-stat signal transduction pathway through the eyes of cytokine class II receptor complexes. Oncogene 19(21):2557–2565

    Article  CAS  PubMed  Google Scholar 

  17. Logsdon NJ, Jones BC, Josephson K, Cook J, Walter MR (2002) Comparison of interleukin-22 and interleukin-10 soluble receptor complexes. J Interf Cytokine Res 22(11):1099–1112

    Article  CAS  Google Scholar 

  18. Ding Y, Qin L, Zamarin D, Kotenko SV, Pestka S, Moore KW et al (2001) Differential IL-10R1 expression plays a critical role in IL-10-mediated immune regulation. J Immunol 167(12):6884–6892

    Article  CAS  PubMed  Google Scholar 

  19. Arnett F, Edworthy C (1988) The American rheumatism association revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324

    Article  CAS  PubMed  Google Scholar 

  20. Taylor PC (2003) Anti-cytokines and cytokines in the treatment of rheumatoid arthritis. Curr Pharm Des 9:1095–1106

    Article  CAS  PubMed  Google Scholar 

  21. Lubberts E, van den Berg WB (2001) Potential of modulatory cytokines in the rheumatoid arthritis process. Drug News Perspect 14:517–522

    Article  CAS  PubMed  Google Scholar 

  22. Wolk K, Witte E, Reineke U, Witte K, Friedrich M, Sterry W et al (2005) Is there an interaction between interleukin-10 and interleukin-22? Genes Immun 6(1):8–18

    CAS  PubMed  Google Scholar 

  23. Reineke U, Schneider-Mergener J, Glaser RW, Stigler RD, Seifert M, Volk HD et al (1999) Evidence for conformationally different states of interleukin-10: binding of a neutralizing antibody enhances accessibility of a hidden epitope. J Mol Recognit 12(4):242–248

    Article  CAS  PubMed  Google Scholar 

  24. Yoon SI, Logsdon NJ, Sheikh F, Donnelly RP, Walter MR (2006) Conformational changes mediate interleukin-10 receptor 2 (IL-10R2) binding to IL-10 and assembly of the signaling complex. J Biol Chem 281(46):35088–35096

    Article  CAS  PubMed  Google Scholar 

  25. Neidhart M, Jüngel A, Ospelt C, Michel BA, Gay RE, Gay S (2005) Deficient expression of interleukin-10 receptor alpha chain in rheumatoid arthritis synovium: limitation of animal models of inflammation. Arthritis Rheum 52(10):3315–3318

    Article  PubMed  Google Scholar 

  26. Hermann J, Gruber S, Neufeld JB, Grundtner P, Graninger M, Graninger WB et al (2009) IL10R1 loss-of-function alleles in rheumatoid arthritis and systemic lupus erythematosus. Clin Exp Rheumatol 27(4):603–608

    CAS  PubMed  Google Scholar 

  27. Hussain SK, Madeleine MM, Johnson LG, Du Q, Galloway DA, Daling JR et al (2013) Nucleotide variation in IL-10 and IL-12 and their receptors and cervical and vulvar cancer risk: a hybrid case-parent triad and case-control study. Int J Cancer 133(1):201–213

    Article  CAS  PubMed  Google Scholar 

  28. Bi X, Zheng T, Lan Q, Xu Z, Chen Y, Zhu G et al (2012) Genetic polymorphisms in IL10RA and TNF modify the association between blood transfusion and risk of non-Hodgkin lymphoma. Am J Hematol 87(8):766–769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (81473058).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Dong-Qing Ye.

Ethics declarations

Disclosures

None.

Additional information

Xiao-Ke Yang and Peng Li contributed equally to this work and should be considered co-first authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, XK., Li, P., Li, S. et al. Genetic variant of IL-10RA and susceptibility to rheumatoid arthritis in a Chinese population. Clin Rheumatol 36, 825–830 (2017). https://doi.org/10.1007/s10067-016-3449-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-016-3449-9

Keywords

Navigation