CCR2 V64I Genotyping: Impact on end stage renal disease development, progression and renal transplantation outcome
DOI:
https://doi.org/10.56511/JIPBS.2018.v5.i04.pp05-11Abstract
Chemokine receptor 2 (CCR2) may have an impact on end stage renal disease (ESRD) development in children as well as renal allograft survival. Objective: Detection of the relevance of the CCR2 V64I gene polymorphism to the development and progression of ESRD and its impact on graft rejection in transplanted children. Methods: Genotyping for CCR2 V64I was done for seventy five children with end-stage renal disease (ESRD) [50 treated with renal transplantation and 25 with hemodialysis] and seventy five healthy children by polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) analysis. Results: The CCR2 V64I displayed significantly higher frequencies among transplantation, hemodialysis, ESRD-patients as well as those with acute rejection when compared with the control subjects (P value <0.001for all).The mutant A allele displayed statistically significant frequencies in all groups when compared with the control group (P value < 0.001). Moreover, carriers of mutant A allele had increased risk of developing both ESRD and acute rejection after transplantation [32.4 times more risk to develop ESRD (OR 32.4; 95% CI 14.1-74.1, P value <0.001) and 5.1 times more risk to suffer acute graft rejection (OR 5.1; 95% CI 1.6-16.1, P value 0.03)]. Conclusion: The frequency of the A allele of the CCR2 V64I genotypes was significantly higher among children with ESRD & those with acute graft rejection and this allele might be considered a risk marker for pediatric ESRD development as well as a predictor of graft rejection.
Keywords:
CCR2 V64I genotypes, ESRD, Renal graft rejection, Hemodialysis, RFLP, Gene polymorphism, Children, Renal TransplantationDownloads
References
Elghoroury EA, Fadel FI , Elshamaa MF , Kandil D et al. Klotho G-395A gene polymorphism: Impact on the progression of the end stage renal disease and the development of cardiovascular complications in children on dialysis. Pediatr Nephrol. 2018. doi: 10.1007/s00467-017-3877.
Matas AJ, Smith JM, Skeans MA, Thompson B, et al. OPTN/SRTR 2012 Annual Data Report: kidney. Am J Transplant. 2014; 1:11-44.
Kim, H.L., Lee, D.S., Yang, S.H., Lim, C.S., et al. The polymorphism of monocyte chemoattractant protein-1 is associated with the renal disease of SLE. American Journal of Kidney Diseases 2002; 40:1146.
Gorg Y, Sfar I, Jendoubi-Ayed S, M Makhlouf A, et al. Allgraft renal rejection and chemokine polymorphism. Saudi Journal of kidney transplantation and diseases 2011; 22(1): 18-23.
SinghV, Srivastava N, Srivastava P, Mittal R. Impact of CCL2 and Its Receptor CCR2 Gene Polymorphism in North Indian Population: A Comparative Study in Different Ethnic Groups Worldwide. Ind J Clin Biochem. 2013; 28(3):259 – 264.
You H , Gao T , Raup-Konsavage WM , Cooper TK , et al. Podocyte-specific chemokine (C-C motif) receptor 2 over expression mediates diabetic renal injury in mice. Kidney Int. 2017; 91(3): 671 – 682.
Abdi R, Huong T, Sahagun A, Murphy P, et al. Chemokine Receptor Polymorphism and Risk of Acute Rejection in Human Renal Transplantation. J Am Soc Nephrol. 2002; 13: 754 – 758.
Ferreira-Fernandes H, Santos A, Motta F, Canalle R, et al. Prevalence of CCR5 Δ 32 and CCR2-V64I polymorphisms in a mixed population from northeastern Brazil. Genetics and Molecular Research 2015; 14(4): 1171011718.
Mula-Abed W., Rasadi Kh., and Al-Riyami D. Estimated Glomerular Filtration Rate (eGFR): A Serum Creatinine-Based Test for the Detection of Chronic Kidney Disease and its Impact on Clinical Practice. Oman Med J. 2012; 27(2): 108 – 113.
Stallone G, Infante B, Schena A, et al. Rapamycin for treatment of chronic allograft nephropathy in renal transplant patients. J Am Soc Nephrol 2005; 16:3755.
Solez K, Colvin RB, Racusen LC, Haas M, Sis B, Mengel M, Halloran PF, Baldwin W, Banfi G, Collins AB, Cosio F, David DS, Drachenberg C, Einecke G, Fogo AB, Gibson IW, Glotz D, Iskandar SS, Kraus E, Lerut E, Mannon RB, Mihatsch M, Nankivell BJ, Nickeleit V: Banff ’ 07 classification of renal allograft pathology: updates and future directions. Am J Transplant 2008; 8: 753 – 760.
Sezgin I, Koksal B, Bagci G, Kurtulgan H and Ozdemir O. CCR2 Polymorphism in Chronic Renal Failure Patients Requiring Long-Term Hemodialysis. Intern Med 50: 2011; 2457-2461.
Bakos E, Thaiss C, Kramer M, Cohen S, et al. CCR2 Regulates the Immune Response by Modulating the Interconversion and Function of Effector and Regulatory T Cells. J Immunol. 2017; 1601458; DOI: https://doi.org/10.4049/jimmunol.1601458 .
Gao J, Liu X, Wei L, Niu D, et al. Genetic variants of MCP-1 and CCR2 genes and IgA nephropathy risk. Oncotarget . 2016; 7(47): 77950 – 77957.
Braga T , Correa-Costa M , Silva RC , Cruz MC et al. CCR2 contributes to the recruitment of monocytes and leads to kidney inflammation and fibrosis development. Inflammopharmacology 2018; 26(2):403-411.
Mannon R. Macrophages: Contributors to Allograft Dysfunction, Repair or Innocent Bystanders?. Curr Opin Organ Transplant 2012; 17(1): 20 – 25.
Li L , Huang L, Sung J, Vergis A, et al. The chemokine receptors CCR2 and CX3CR1 mediate monocyte/macrophage trafficking in kidney ischemia – reperfusion injury. Kidney Int. 2008; 74(12): 1526 – 1537.
Vielhauer V, Eis V, Schlondorff D, Anders HJ. Identifying chemokines as therapeutic targets in renal disease: lessons from antagonist studies and knockout mice. Kidney Blood Press Res. 2004; 27: 226-238.
Elghoroury E, Fadel F, Farouk H, Elshamaa M, et al. Association of variable number tandem repeats polymorphismin the IL-4 gene with endstage renal disease in children. The Egyptian Journal of Medical Human Genetics 2018; 19(3):191-195.
Nakajima K, Tanaka Y, Nomiyama T, Chemokine Receptor Genotype Is Associated With Diabetic Nephropathy in Japanese with Type 2 Diabetes. Diabetes 2002; 51(1): 238-242.
Ana M. Valdes, Megan L. Wolfe, Eamonn J, et al. Val64Ile Polymorphism in the C-C Chemokine Receptor 2 Is Associated With Reduced Coronary Artery Calcification. Arterioscler Thromb Vasc Biol. 2002; 22:1924 1928.
Lim, S. Y., Yuzhalin, A. E., Gordon-Weeks, A. N. and Muschel, R. Targeting the CCL2-CCR2 signaling axis in cancer metastasis. Oncotarget 2016; 7:28697-28710.
Kuper C, Beck FX, Neuhofer W. Autocrine MCP-1/CCR2 signaling stimulates proliferation and migration of renal carcinoma cells. Oncol Lett. 2016; 12: 2201 – 9.
Lalor, P.F. & Adams, D.H. Lymphocyte homing to allografts. Transplantation 2001; 70: 1131.
Fife BT, Huffnagle GB, Kuziel WA, Karpus WJ: CC chemokine receptor 2 is critical for induction of experimental autoimmune encephalomyelitis. J Exp Med. 2000; 192: 899 – 905.
Kang SW, Park SJ, Kim YH, et al. Association of MCP-1 and CCR2 polymorphisms with the risk of late acute rejection after renal transplantation in Korean patients. Int J Immunogenet 2007; 35:25-31.
Simeoni E, Vassalli G, Seydoux C, Ramsay D, et al. CCR5, RANTES and CX3CR1 polymorphisms: possible genetic links with acute heart rejection. Transplantation 2005; 80:1309 – 15.
Schroppel B, Fischereder M, Ashkar R, Lin M, Kramer BK, et al. The impact of polymorphisms in chemokine and chemokine receptors on outcomes in liver transplantation. Am J Transplant. 2002; 2:640 – 5.
Published
How to Cite
Issue
Section
Copyright (c) 2018 Eman A. Elghoroury, Manal F. Elshamaa, Fatina I. Fadel, Dina Kandil, Hebatallah Farouk, Solaf Kamel, Eman Mahmoud, Marwa M Nabhan

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.




Journal of Innovations in Pharmaceutical and Biological Sciences is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Based on a work at