Impact of Chemokine Receptor CCR2 and CCR5 Gene Polymorphism on Allograft Outcome in North Indian Renal Transplant Recipients

The CC chemokine receptors, CCR2 and CCR5, contribute to the trafficking of leucocytes into the sites of the immune response in transplanted kidney. Therefore, the inter-individual differences in CCR2 and CCR5 gene expression, due to single-nucleotide polymorphism, have the potential to influence various immune responses within the graft, eventually deciding the allograft outcome. In this study, we genotyped 296 North Indian renal transplant recipients and 277 healthy controls for CCR2V64I and CCR5-Delta 32 polymorphisms by sequence-specific primers and restriction fragment length polymorphism and examined their association with allograft outcome. The frequency of CCR2+/64I (heterozygous) and CCR2-64I/64I (homozygous mutant) genotype were comparatively higher in non-rejecters when compared with transplant recipients experiencing one or more than one rejection episode (20.4% versus 8.2%), thereby resulting in a significantly reduced risk of allograft rejection (OR = 0.331, P = 0.026). The Kaplan-Meier curve also suggested higher mean time for the first rejection episode in CCR2-64I allele carriers (32.83 +/- 1.36 months) when compared with CCR2+/+ recipients (28.09 +/- 0.93 months, log P = 0.027). The CCR5-Delta 32 variant had no profound effect on allograft outcome. In conclusion, our study confirmed CCR2-64I allele to be associated with reduced risk for allograft rejection in North Indian transplant recipients influencing allograft outcome.