Skip to main content

Advertisement

Log in

Polymorphism in interleukin 21 gene is associated with decreased susceptibility to diffuse large B cell lymphoma

  • Research Article
  • Published:
Tumor Biology

Abstract

Interleukin 21 (IL-21) plays a key role in innate and adaptive immunity. Polymorphisms in IL-21 gene may be greatly involved in various diseases. The aim of the study was to investigate the association between IL-21 genetic polymorphisms and the susceptibility to diffuse large B cell lymphoma (DLBCL). IL-21 −2498G/A and +78A/G polymorphisms were examined in 221 DLBCL patients and 243 healthy controls. We found that distributions of −2498GA genotype and −2498AA genotype were clearly decreased in DLBCL cases compared to healthy donors (odds ratio [OR] = 0.71, 95 % confidence interval [CI] = 0.43–0.92, P = 0.021; OR = 0.36, 95 % CI = 0.15–0.48, P < 0.001; data were adjusted for age and sex). Stratification analyses revealed that patients with advanced Ann Arbor stages (III + IV) had further decreased percentage of −2498AA genotype than those with primary stages (OR = 0.31, 95 % CI = 0.13–0.87, P = 0.023; data were adjusted for age and sex). In addition, we evaluated the possible effect of IL-21 polymorphisms on gene expression by examining serum level of IL-21 in patients and controls. Data revealed that subjects carrying −2498AA genotype had significantly higher serum level of IL-21 than those with GG genotype or GA genotype. These data suggest that IL-21 −2498G/A polymorphism is associated with decreased susceptibility to DLBCL and may increase serum level of IL-21.

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.

Fig. 1

Similar content being viewed by others

References

  1. Montgomery ND, Fedoriw Y. Pathology consultation on intermediate-to-large B-cell lymphomas. Am J Clin Pathol. 2014;141:305–17.

    Article  PubMed  Google Scholar 

  2. Morin RD, Gascoyne RD. Newly identified mechanisms in B-cell non-Hodgkin lymphomas uncovered by next-generation sequencing. Semin Hematol. 2013;50:303–13.

    Article  CAS  PubMed  Google Scholar 

  3. Puvvada S, Kendrick S, Rimsza L. Molecular classification, pathway addiction, and therapeutic targeting in diffuse large B cell lymphoma. Cancer Genet. 2013;206:257–65.

    Article  CAS  PubMed  Google Scholar 

  4. Cha Z, Zang Y, Guo H, Gu H, Tu X, et al. Fibroblast growth factor receptor 4 polymorphisms and the prognosis of non-Hodgkin lymphoma. Mol Biol Rep. 2014;41:1165–70.

    Article  CAS  PubMed  Google Scholar 

  5. Gao L, Feng Z, Li Q, Li L, Chen L, et al. Fibroblast growth factor receptor 4 polymorphism is associated with increased risk and poor prognosis of non-Hodgkin’s lymphoma. Tumour Biol. 2014;35:2997–3002.

    Article  CAS  PubMed  Google Scholar 

  6. Zhou C, Cui S, Zhou R, Dou L. Association between interleukin-4–590C>T polymorphism and non-Hodgkin’s lymphoma risk. Tumour Biol. 2014;35:3041–5.

    Article  CAS  PubMed  Google Scholar 

  7. Mehta DS, Wurster AL, Grusby MJ. Biology of IL-21 and the IL-21 receptor. Immunol Rev. 2004;202:84–95.

    Article  CAS  PubMed  Google Scholar 

  8. Leonard WJ, Spolski R. Interleukin-21: a modulator of lymphoid proliferation, apoptosis and differentiation. Nat Rev Immunol. 2005;5:688–98.

    Article  CAS  PubMed  Google Scholar 

  9. Kasaian MT, Whitters MJ, Carter LL, Lowe LD, Jussif JM, et al. IL-21 limits NK cell responses and promotes antigen-specific T cell activation: a mediator of the transition from innate to adaptive immunity. Immunity. 2002;16:559–69.

    Article  CAS  PubMed  Google Scholar 

  10. Eskelund CW, Nederby L, Thysen AH, Skovbo A, Roug AS, et al. Interleukin-21 and rituximab enhance NK cell functionality in patients with B-cell chronic lymphocytic leukaemia. Leuk Res. 2011;35:914–20.

    Article  CAS  PubMed  Google Scholar 

  11. Ghalamfarsa G, Jadidi-Niaragh F, Hojjat-Farsangi M, Asgarian-Omran H, Yousefi M, et al. Differential regulation of B-cell proliferation by IL21 in different subsets of chronic lymphocytic leukemia. Cytokine. 2013;62:439–45.

    Article  CAS  PubMed  Google Scholar 

  12. Jahrsdorfer B, Blackwell SE, Wooldridge JE, Huang J, Andreski MW, et al. B-chronic lymphocytic leukemia cells and other B cells can produce granzyme B and gain cytotoxic potential after interleukin-21-based activation. Blood. 2006;108:2712–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Sarosiek KA, Malumbres R, Nechushtan H, Gentles AJ, Avisar E, et al. Novel IL-21 signaling pathway up-regulates c-Myc and induces apoptosis of diffuse large B-cell lymphomas. Blood. 2010;115:570–80.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Strengell M, Sareneva T, Foster D, Julkunen I, Matikainen S. IL-21 up-regulates the expression of genes associated with innate immunity and Th1 response. J Immunol. 2002;169:3600–5.

    Article  PubMed  Google Scholar 

  15. Song H, Chen L, Cha Z, Bai J. Interleukin 2 gene polymorphisms are associated with non-Hodgkin lymphoma. DNA Cell Biol. 2012;31:1279–84.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Song H, Tong D, Cha Z, Bai J. C-X-C chemokine receptor type 5 gene polymorphisms are associated with non-Hodgkin lymphoma. Mol Biol Rep. 2012;39:8629–35.

    Article  CAS  PubMed  Google Scholar 

  17. Lin J, Peng Y, Zhou B, Dou Q, Li Y, et al. Genetic association of IL-21 polymorphisms with dilated cardiomyopathy in a Han Chinese population. 2014. Herz.

  18. Xiao M, Hu S, Tang J, Zhang L, Jiang H. Interleukin (IL)-21 promoter polymorphism increases the risk of thyroid cancer in Chinese population. Gene. 2014;537:15–9.

    Article  CAS  PubMed  Google Scholar 

  19. You Y, Deng J, Zheng J, Hu M, Li N, et al. IL-21 gene polymorphism is associated with the prognosis of breast cancer in Chinese populations. Breast Cancer Res Treat. 2013;137:893–901.

    Article  CAS  PubMed  Google Scholar 

  20. Zhang J, Xiao WX, Zhu YF, Muhali FS, Xiao L, et al. Polymorphisms of interleukin-21 and interleukin-21-receptor genes confer risk for autoimmune thyroid diseases. BMC Endocr Disord. 2013;13:26.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Mizuguchi M, Asao H, Hara T, Higuchi M, Fujii M, et al. Transcriptional activation of the interleukin-21 gene and its receptor gene by human T-cell leukemia virus type 1 Tax in human T-cells. J Biol Chem. 2009;284:25501–11.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Cha Z, Gu H, Guo H, Tu X, Zang Y, et al. Effect of interleukin 21 and its receptor on CD8 T cells in the pathogenesis of diffuse large B-cell lymphoma. Oncol Lett. 2014;8:421–5.

    CAS  PubMed Central  PubMed  Google Scholar 

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jie Li.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, J., Mai, J. Polymorphism in interleukin 21 gene is associated with decreased susceptibility to diffuse large B cell lymphoma. Tumor Biol. 35, 11295–11300 (2014). https://doi.org/10.1007/s13277-014-2440-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-014-2440-9

Keywords

Navigation