41-OR

Abstract

Acute and chronic allograft rejections are important causes of morbidity following kidney transplantation that ultimately influence long term graft function. Cytokines are the key molecules known to regulate immune response towards alloantigen determining graft rejection or tolerance. Genetic variability including single nucleotide polymorphisms (SNPs) in the promoter and coding region of these genes is known to influence cytokine expression, and could therefore significantly impact the outcome of the alloimmune response. In this study, SNPs in cytokine genes namely Interleukin (IL)-12 (−1188 C/A), interferon (IFN)-g (+874 A/T), transforming growth factor (TGF)-b (C/T codon 10, G/C codon 25), tumor necrosis factor (TNF)-a (G/A −308, G/A −238), IL2 (T/G −330, G/T +160), and IL10 (G/A −1082, C/T −819, C/A −592) were determined in 182 patients undergoing renal transplantation from their live related and unrelated donors. Of these, 50 patients experienced acute rejection episodes (AR), 42 experienced chronic allograft nephropathy (CAN) (25 patients who had previous AR episodes and 17 without any AR episodes), while the remaining 115 patients had well functioning grafts (WFG). The high producer genotype TT of IFN-g showed a strong association with development of AR; while the AA genotype (low producer) conferred protection from AR (p < 0.0001) and CAN (p = 0.007). Similarly, genotype GG at codon 25 (high producer) of TGF-b, was associated with AR episodes (p < 0.05) and CAN (p < 0.05). The study highlights the clinical relevance of cytokine gene polymorphism as an important biomarker to predict acute rejection episodes and chronic allograft nephropathy following live donor kidney transplantation.