Skip to main content

Advertisement

SpringerLink
Log in

Chemokine (CCR) and fractalkine (CX3CR) receptors and end stage renal disease

  • Original Research Paper
  • Published:
Inflammation Research Aims and scope Submit manuscript

Abstract

Objective and design

Genetic polymorphisms of chemokines and their receptors were reported to be independent risk factors for inflammation associated disease. We explored the role of CCR5-Δ32, CCR5–G59029A, CX3CR1 V249I and T280M gene polymorphisms as susceptibility for end stage renal disease (ESRD).

Subjects and methods

We genotyped 258 ESRD and 569 healthy controls by sequence-specific primers and RFLP and examined their association.

Results

There was significant difference in genotype frequencies of CCR5–G59029A (p = 0.005), and CX3CR1 V249I (p < 0.0001) between ESRD and controls. No homozygous individuals were observed for CCR5-Δ32. The haplotype analysis of all four studied genes reveled that haplotype +/A/T/I was more significant in patients and associated with higher risk (OR = 2.95) of ESRD. Further, the haplotype of CX3CR1 (T280M, V249I) gene showed 3.6-fold higher in an individual carrying T/I haplotype. No risk was seen for CCR5 haplotypes.

Conclusions

These results highlight the role of CCR5 and CX3CR1 in ESRD.

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. Bursill CA, Channon KM, Greaves DR. The role of chemokines in atherosclerosis: Recent evidence from experimental models and population genetics. Curr Opin Lipidol. 2004;15:145–9.

    Article  PubMed  CAS  Google Scholar 

  2. Zernecke A, Shagdarsuren E, Weber C. Chemokines in atherosclerosis: An update. Arterioscler Thromb Vasc Biol. 2008;28:1897–908.

    Article  PubMed  CAS  Google Scholar 

  3. Raport CJ, Gosling J, Schweickart VL, Gray PW, Charo IF. Molecular cloning and functional characterization of a novel human CC chemokine receptor (CCR5) for RANTES, MIP-1beta, and MIP-1alpha. J Biol Chem. 1996;271:17161–6.

    Article  PubMed  CAS  Google Scholar 

  4. Simeoni E, Vassalli G, Seydoux C, et al. CCR5, RANTES and CX3CR1 polymorphisms: possible genetic links with acute heart rejection. Transplantation. 2005;80:1309–16.

    Article  PubMed  CAS  Google Scholar 

  5. Schr¨oppel B, Fischereder M, Lin M, et al. Analysis of gene polymorphisms in the regulatory region of MCP-1, RANTES, and CC5 in liver transplant recipients. J Clin Immunol. 2002;22:381–5.

    Article  Google Scholar 

  6. Hoffmann S, Park J, Jacobson LM, et al. Donor genomics influence graft events: the effect of donor polymorphisms on acute rejection and chronic allograft nephropathy. Kidney Int. 2004;66:1686–93.

    Article  PubMed  CAS  Google Scholar 

  7. Yigit B, Bozkurt N, Berber I, et al. Analysis of CC chemokine receptor 5 and 2 polymorphisms and renal transplant survival. Cell Biochem Funct. 2007;25:423–6.

    Article  PubMed  CAS  Google Scholar 

  8. Abdi R, Tran TB, Sahagun-Ruiz A, Murphy PM, Brenner BM, Milford EL, Mcdermott DH. Chemokine receptor polymorphism and risk of acute rejection in human renal transplantation. J Am Soc Nephrol. 2002;13:754–8.

    PubMed  CAS  Google Scholar 

  9. Schlondorff D, Nelson PJ, Lucknow B, Banas B. Chemokines and renal disease. Kidney Int. 1997;51:610–21.

    Article  PubMed  CAS  Google Scholar 

  10. Fischereder M, Luckow B, Hocher B, et al. CC chemokine receptor 5 and renal-transplant survival. Lancet. 2001;23:1758–61.

    Article  Google Scholar 

  11. Takacova M, Nogova P, Habekova M, et al. Prevalence of a 32 bp deletion in the gene for human immunodeficiency virus 1 co-receptor ccr5 in Slovak population. Acta Virol. 2008;52:261–4.

    PubMed  CAS  Google Scholar 

  12. Thio CL, Astemborski J, Thomas R, et al. Interaction between RANTES promoter variant and CCR5d32 favors recovery from hepatitis B. J Immunol. 2008;181:7944–7.

    PubMed  CAS  Google Scholar 

  13. Wang F, Xiul MH, Zhou DF, et al. The CCR5 32-bp deletion allele is rare in a Chinese population. Schizophr Res. 2008;101:341–3.

    Article  PubMed  Google Scholar 

  14. Horuk R. Chemokine receptors. Cytokine Growth Factor Rev. 2001;12:313–35.

    Article  PubMed  CAS  Google Scholar 

  15. Hancock WW. Chemokines and transplant immunobiology. J Am Soc Nephrol. 2002;13:821–4.

    PubMed  CAS  Google Scholar 

  16. Faure S, Meyer L, Costagliola D, et al. Rapid progression to AIDS among HIV+ individuals with an allelic variants of the CX3CR1 chemokine receptor. Science. 2000;287:2274–7.

    Article  PubMed  CAS  Google Scholar 

  17. Moatti D, Faure S, Fumeron F, Amara Mel-W, Seknadji P, McDermott DH, Debre P, Aumont MC, Murphy PM, de Prost D, Combadiere C. Polymorphism in the fractalkine receptor CX3CR1 as a genetic risk factor for coronary artery disease. Blood. 2001;97:1925–8.

    Article  PubMed  CAS  Google Scholar 

  18. Balistreri CR, Caruso C, Grimaldi MP, Listi F, Vasto S, Orlando V, Campagna AM, Lio D, Candore G. CCR5 receptor: Biologic and genetic implications in age-related diseases. Ann N Y Acad Sci. 2007;1100:162–72.

    Article  PubMed  CAS  Google Scholar 

  19. Pai JK, Kraft P, Cannuscio CC, Manson JE, Rexrode KM, Albert CM, Hunter D, Rimm EB. Polymorphisms in the CC-chemokine receptor-2 (CCR2) and -5 (CCR5) genes and risk of coronary heart disease among US women. Atherosclerosis. 2006;186:132–9.

    Article  PubMed  CAS  Google Scholar 

  20. Manchanda PK, Singh R, Mittal RD. Cytokine (IL-10–1082 and -819) and chemokine receptor (CCR2 and CCR5) gene polymorphism in North Indian patients with end-stage renal disease. DNA Cell Biol. 2009;28:177–83.

    Article  PubMed  CAS  Google Scholar 

  21. Muntinghe FL, Verduijn M, Zuurman MW, Grootendorst DC, Carrero JJ, Qureshi AR, Luttropp K, Nordfors L, Lindholm B, Brandenburg V, Schalling M, Stenvinkel P, Boeschoten EW, Krediet RT, Navis G, Dekker FW. CCR5 deletion protects against inflammation-associated mortality in dialysis patients. J Am Soc Nephrol. 2009;20:1641–9.

    Article  PubMed  CAS  Google Scholar 

  22. Furuta T, Salto T, Ootaka T, Soma J, Obara K, Abe K, Yoshinaga K. The role of macrophages in diabetic glomerulosclerosis. Am J Kidney Dis. 1993;21:480–5.

    PubMed  CAS  Google Scholar 

  23. Cha RH, Yang SH, Kim HS, Kim SM, Park MH, Ha J, Kim YS. Genetic interactions between the donor and the recipient for susceptibility to acute rejection in kidney transplantation: polymorphisms of CCR5. Nephrol Dial Transplant. 2009;24:2919–25.

    Article  PubMed  CAS  Google Scholar 

  24. Böger CA, Fischereder M, Deinzer M, Aslanidis C, Schmitz G, Stubanus M, Banas B, Krüger B, Riegger GA, Krämer BK. RANTES gene polymorphisms predict all-cause and cardiac mortality in type 2 diabetes mellitus hemodialysis patients. Atherosclerosis. 2005;183:121–9.

    Article  PubMed  Google Scholar 

  25. Ding X, Patel M, Chan CC. Molecular pathology of age-related macular degeneration. Prog Retin Eye Res. 2009;28:1–18.

    Article  PubMed  CAS  Google Scholar 

  26. Lu Y, Nerurkar VR, Dashwood WM, Woodward CL, Ablan S, Shikuma CM, Grandinetti A, Chang H, Nguyen HT, Wu Z, Yamamura Y, Boto WO, Merriwether A, Kurata T, Detels R, Yanagihara R. Genotype and allele frequency of a 32-base pair deletion mutation in the CCR5 gene in various ethnic groups: absence of mutation among Asians and Pacific Islanders. Int J Infect Dis. 1999;3:186–91.

    Article  PubMed  CAS  Google Scholar 

  27. DeVries ME, Cao H, Wang J, Xu L, Kelvin AA, Ran L, Chau LA, Madrenas J, Hegele RA, Kelvin DJ. Genomic organization and evolution of the CX3CR1/CCR8 chemokine receptor locus. J Biol Chem. 2003;278:11985–94.

    Article  PubMed  CAS  Google Scholar 

  28. Rathore A, Chatterjee A, Sivarama P, Yamamoto N, Singhal PK, Dhole TN. Association of CCR5–59029 A/G and CCL3L1 copy number polymorphism with HIV type 1 transmission/progression among HIV type 1-seropositive and repeatedly sexually exposed HIV type 1-seronegative North Indians. AIDS Res Hum Retroviruses. 2009;25:1149–56.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

G. Tripathi is thankful to the Jawaharlal Nehru Memorial Fund, New Delhi, for awarding junior research fellowship. We are thankful to P.B. Vinod for providing us the clinical details.

Author information

Authors and Affiliations

  1. Department of Urology, Chatrapati Sahuji Maharaj Medical University, Lucknow, India

    Gaurav Tripathi & Satya Narayan Sankhwar

  2. Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, UP, 226014, India

    Minal Borkar & Suraksha Agrawal

  3. Department of Nephrology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India

    Raj Kumar Sharma

Authors
  1. Minal Borkar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gaurav Tripathi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Raj Kumar Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Satya Narayan Sankhwar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Suraksha Agrawal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Suraksha Agrawal.

Additional information

Responsible Editor: Andras Falus.

M. Borkar, G. Tripathi and S. Agrawal have contributed equally to this work.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 73 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Borkar, M., Tripathi, G., Sharma, R.K. et al. Chemokine (CCR) and fractalkine (CX3CR) receptors and end stage renal disease. Inflamm. Res. 60, 399–407 (2011). https://doi.org/10.1007/s00011-010-0284-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00011-010-0284-3

Keywords

Search

Navigation