Back to Journals » Biologics: Targets and Therapy » Volume 2 » Issue 4

Association of pro/anti-inflammatory cytokine gene variants in renal transplant patients with allograft outcome and cyclosporine immunosuppressant levels

Authors Manchanda PK, Kumar A, Sharma RK, Goel H, Mittal R

Published 5 December 2008 Volume 2008:2(4) Pages 875—884

DOI https://doi.org/10.2147/BTT.S2459

Parmeet Kaur Manchanda, Anant Kumar, Raj K Sharma, Himanshu Goel, Rama Devi Mittal

Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, Uttar Pradesh, India

Abstract: T-helper (Th) type 1/Th2 cytokines are key mediators in induction/effecter phases of all immune and inflammatory responses playing role in acute/chronic renal allograft rejection. Association studies lead to identification of patient risk profiles enabling individualization of level of immunosuppressions. We investigated the association of allograft rejection with interleukin-2 (IL-2), IL-4, IL-6, tumor necrosis factor-α (TNF-α) –308, transforming growth factor-β (TGF-β) (C-del, codon 10 and 25) gene variants in 184 renal transplant recipients and 180 controls. These cytokine genotypes were also evaluated with cyclosporine levels (C2) at one month in 135 stable recipients. High producing genotypes B1B1 of IL-4 and AA of TNF-α −308 showed significant association with rejection of allograft. The dose-adjusted C2 levels were significantly lower in patients with the high producing genotype T/T of IL-2 and heterozygous G/C of TGF-β codon 25 (P = 0.012 and 0.010, respectively). Haplotype frequencies were comparable in subjects for TGF-β codon-10 and 25. Combined inter-gene interaction showed high risk for rejection in recipients with high producing genotype B1B1 of IL-4 and AA of TNF-α and high TNF-α (AA) with low TGF-β (CC or Pro/Pro). In conclusion, association of IL-4 VNTR and TNF-α –308 suggested the involvement of these cytokines contributing to pathogenesis of allograft rejection. Recipients with TT genotype of IL-2 and GC of TGF-β codon 25 having low C2 levels may require higher cyclosporine dosage. Combined analysis of gene-gene interaction demonstrated synergistic effect of cytokines increasing risk for rejection. Thus, this information may help in pre-assessment of allograft outcome and to optimize cyclosporine therapy in post-transplant patients.

Keywords: cytokines, renal transplant, polymorphism, ARMS–PCR, PCR–RFLP, cyclosporine

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]