Skip to main content
SpringerLink
Log in

Association between the rs3751143 polymorphism of P2RX7 gene and chronic lymphocytic leukemia: A meta-analysis

  • Review Article
  • Published:
Purinergic Signalling Aims and scope Submit manuscript

Abstract

Objectives

Meta-analysis was used to determine the association between rs3751143 polymorphism of P2RX7 gene and the risk of chronic lymphocytic leukemia (CLL).

Methods

Search for published articles about the association between the rs3751143 and CLL in PubMed, MEDINE, Web of Science, and Embase databases, with a calculated odds ratio of (OR) and 95% confidence interval (95%CI).

Results

A total of 1184 cases and 1725 controls in 8 studies were pooled together for evaluation of the overall association between rs3751143 and risk of CLL. Allele model (A vs C, p = 0.16, OR = 0.85, 95%CI = 0.71–1.17), homozygous model (AA vs CC, p = 0.07; OR = 0.78, 95%CI = 0.84–1.08), and heterozygous model (AC vs CC, p = 0.76; OR = 0.85; 95%CI = 0.68–0.79) did not show decreased risk of developing CLL. Similarly, dominant model (AA + AC vs. CC: p = 0.58; OR = 1.10, 95%CI = 0.69–1.75), and recessive model (AA vs AC + CC, p = 0.21, OR = 1.18, 95%CI = 0.70–1.99) failed to show decreased risk of developing CLL. However, in familial, heterozygous model (AC vs. CC: p = 0.0006, OR = 0.64, 95%CI = 0.67–1.50) and recessive model (AA vs. AC + CC: p = 0.0017; OR = 1.02, 95%CI = 0.73–2.35) indicated the association between the inheritance of rs3751143 and the risk of developing CLL. In the overall survival prognosis, no significant association between rs3751143 and CLL was detected with relatively high heterogeneity.

Conclusions

Our pooled data indicates that there is a correlation between the inheritance of rs3751143 and the risk of CLL in familial.

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

Fig. 1

Similar content being viewed by others

Data availability

All data generated or analyzed during this study are included in this article. And we have not used other data that has already been published. All the data presented in this article are original results derived from this study.

References

  1. Takizawa J (2017) Chronic lymphocytic leukemia: pathophysiology and current therapy. Rinsho Ketsueki 58:471–479

    PubMed  Google Scholar 

  2. Francesc B, Dalla-Favera R (2019) Chronic lymphocytic leukaemia: from genetics to treatment. Nat Rev Clin Oncol 16:684–701

    Article  Google Scholar 

  3. Zhang WJ, Zhu ZM, Liu ZX (2020) The role and pharmacological properties of the P2X7 receptor in neuropathic pain. Brain Res Bull 155:19–28

    Article  CAS  Google Scholar 

  4. Alves LA, Bezerra RJ, Faria RX, Ferreira L, da Silva Frutuoso V (2013) Physiological roles and potential therapeutic applications of the P2X7 receptor in inflammation and pain. Molecules. 18:10953–10972

    Article  CAS  Google Scholar 

  5. Arandjelovic S, McKenney KR, Leming SS et al (2012) ATP induces protein arginine deiminase 2-dependent citrullination in mast cells through the P2X7 purinergic receptor. J Immunol 189:4112–4122

    Article  CAS  Google Scholar 

  6. Collo G, Neidhart S, Kawashima E, Kosco-Vilbois M, North RA, Buell G (1997) Tissue distribution of the P2X7 receptor. Neuropharmacology. 36:1277–1283

    Article  CAS  Google Scholar 

  7. Zhang XJ, Zheng GG, Ma XT, Yang YH, Li G, Rao Q, Nie K, Wu KF (2004) Expression of P2X7 in human hematopoietic cell lines and leukemia patients. Leuk Res 28:1313–1322

    Article  CAS  Google Scholar 

  8. Feng W, Yang X, Wang L et al (2019) P2X7 promotes the progression of MLL-AF9 induced acute myeloid leukemia by upregulation of Pbx3. Haematologica. 2020:243360

    Google Scholar 

  9. Salaro E, Rambaldi A, Falzoni S, Amoroso FS, Franceschini A, Sarti AC, Bonora M, Cavazzini F, Rigolin GM, Ciccone M, Audrito V, Deaglio S, Pelegrin P, Pinton P, Cuneo A, di Virgilio F (2016) Involvement of the P2X7-NLRP3 axis in leukemic cell proliferation and death. Sci Rep 6:26280

    Article  CAS  Google Scholar 

  10. Ozdemir FA, Deniz Erol VK, Hüseyin Y et al (2014) Lack of association of 1513 a/C polymorphism in P2X7 gene with susceptibility to pulmonary and extrapulmonary tuberculosis. Tuberk Toraks 62:7–11

    Article  Google Scholar 

  11. Dardano A, Falzoni S, Caraccio N, Polini A, Tognini S, Solini A, Berti P, Virgilio FD, Monzani F (2009) 1513A>C polymorphism in the P2X7 receptor gene in patients with papillary thyroid cancer: correlation with histological variants and clinical parameters. J Clin Endocrinol Metab 94:695–698

    Article  CAS  Google Scholar 

  12. Sanz JM, Falzoni S, Morieri ML, Passaro A, Zuliani G, Di Virgilio F (2020) Association of hypomorphic P2X7 receptor genotype with age. Front Mol Neurosci 13:8

    Article  CAS  Google Scholar 

  13. Gu BJ, Zhang W, Worthington RA, Sluyter R, Dao-Ung P, Petrou S, Barden JA, Wiley JS (2001) A Glu-496 to Ala polymorphism leads to loss of function of the human P2X7 receptor. J Biol Chem 276:11135–11142

    Article  CAS  Google Scholar 

  14. Gong M, Dong W, Shi Z, Qiu S, Yuan R (2017) Vascular endothelial growth factor gene polymorphisms and the risk of renal cell carcinoma: evidence from eight case-control studies. Oncotarget. 8:8447–8458

    Article  Google Scholar 

  15. Dao-Ung LP, Fuller SJ, Sluyter R, SkarRatt KK, Thunberg U, Tobin G, Byth K, Ban M, Rosenquist R, Stewart GJ, Wiley JS (2004) Association of the 1513C polymorphism in the P2X7 gene with familial forms of chronic lymphocytic leukaemia. Br J Haematol 125:815–817

    Article  Google Scholar 

  16. Sellick GS, Rudd M, Eve P et al (2004) The P2X7 receptor gene A1513C polymorphism does not contribute to risk of familial or sporadic chronic lymphocytic leukemia. Cancer Epidemiol Biomark Prev 13:1065–1067

    CAS  Google Scholar 

  17. Zintzaras E, Kitsios GD (2009) Synopsis and synthesis of candidate-gene association studies in chronic lymphocytic leukemia: the CUMAGAS-CLL information system. Am J Epidemiol 170:671–678

    Article  Google Scholar 

  18. Wiley JS, Dao-Ung LP, Gu BJ, Sluyter R, Shemon AN, Li C, Taper J, Gallo J, Manoharan A (2002) A loss-of-function polymorphic mutation in the cytolytic P2X7 receptor gene and chronic lymphocytic leukaemia: a molecular study. Lancet. 359:1114–1119

    Article  CAS  Google Scholar 

  19. Nückel H, Frey UH, Dürig J, Dührsen U, Siffert W (2004) 1513A/C polymorphism in the P2X7 receptor gene in chronic lymphocytic leukemia: absence of correlation with clinical outcome. Eur J Haematol 72:259–263

    Article  Google Scholar 

  20. Starczynski J, Pepper C, Pratt G, Hooper L, Thomas A, Hoy T, Milligan D, Bentley P, Fegan C (2003) The P2X7 receptor gene polymorphism 1513 A-->C has no effect on clinical prognostic markers, in vitro sensitivity to fludarabine, Bcl-2 family protein expression or survival in B-cell chronic lymphocytic leukaemia. Br J Haematol 123:66–71

    Article  CAS  Google Scholar 

  21. Zhang LY, Ibbotson RE, Orchard JA, Gardiner AC, Seear RV, Chase AJ, Oscier DG, Cross NCP (2003) P2X7 polymorphism and chronic lymphocytic leukaemia: lack of correlation with incidence, survival and abnormalities of chromosome 12. Leukemia. 17:2097–2100

    Article  CAS  Google Scholar 

  22. Thunberg U, Tobin G, Johnson A, Söderberg O, Padyukov L, Hultdin M, Klareskog L, Enblad G, Sundström C, Roos G, Rosenquist R (2002) Polymorphism in the P2X7 receptor gene and survival in chronic lymphocytic leukaemia. Lancet. 360:1935–1939

    Article  CAS  Google Scholar 

  23. Cabrini G, Falzoni S, Forchap SL et al (2005) A His-155 to Tyr polymorphism confers gain-of-function to the human P2X7 receptor of human leukemic lymphocytes. J Immunol 17:82–89

    Article  Google Scholar 

  24. Goldin LR, Ishibe N, Sgambati M, Marti GE, Fontaine L, Lee MP, Kelley JM, Scherpbier T, Buetow KH, Caporaso NE (2003) A genome scan of 18 families with chronic lymphocytic leukaemia. Br J Haematol 121:866–873

    Article  Google Scholar 

  25. Crowther-Swanepoel D, Mansouri M, Enjuanes A, Vega A, Smedby KE, Ruiz-Ponte C, Jurlander J, Juliusson G, Montserrat E, Catovsky D, Campo E, Carracedo A, Rosenquist R, Houlston RS (2010) Verification that common variation at 2q37.1, 6p25.3, 11q24.1, 15q23, and 19q13.32 influences chronic lymphocytic leukaemia risk. Br J Haematol 150:473–479

    PubMed  Google Scholar 

  26. Xiao W, Gong C, Liu X, Liu Y, Peng S, Luo D, Wang R, Li T, Zhao J, Xiong C, Liang S, Xu H (2019) Association of P2X7R gene with serum lipid profiles in Chinese postmenopausal women with osteoporosis. Climacteric. 22:498–506

    Article  CAS  Google Scholar 

  27. Jørgensen NR, Husted LB, Skarratt KK, Stokes L, Tofteng CL, Kvist T, Jensen JEB, Eiken P, Brixen K, Fuller S, Clifton-Bligh R, Gartland A, Schwarz P, Langdahl BL, Wiley JS (2012) Single-nucleotide polymorphisms in the P2X7 receptor gene are associated with post-menopausal bone loss and vertebral fractures. Eur J Hum Genet 20:675–681

    Article  Google Scholar 

  28. Peng T, Zhong L, Gao J, Wan Z, Fu WP, Sun C (2020) Identification of rs11615992 as a novel regulatory SNP for human P2RX7 by allele-specific expression. Mol Gen Genomics 295:23–30

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We thank Wen-jun Zhang for writing this article and Zheng-ming Zhu for his guidance and support.

Author information

Authors and Affiliations

  1. The Second Affiliated Hospital, Nanchang University, Nanchang, 343000, Jiangxi, China

    Wen-Jun Zhang & Zheng-Ming Zhu

Authors
  1. Wen-Jun Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zheng-Ming Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Wen-jun Zhang carried out the whole study and drafted the manuscript. Zheng-ming Zhu carried out the design of the study and helped revise this paper. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Zheng-Ming Zhu.

Ethics declarations

Competing of interest

The authors declare that they have no competing interests.

Consent for publication

Not applicable.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, WJ., Zhu, ZM. Association between the rs3751143 polymorphism of P2RX7 gene and chronic lymphocytic leukemia: A meta-analysis. Purinergic Signalling 16, 479–484 (2020). https://doi.org/10.1007/s11302-020-09737-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11302-020-09737-8

Keywords

Search

Navigation