The effect of chemokine receptor gene polymorphisms (CCR2V64I, CCR5-59029G>A and CCR5Δ32) on renal allograft survival in Pakistani transplant patients

Background: Gene polymorphisms of the chemokine receptors CCR2 and CCR5 (CCR2V64I, CCR5-59029G>A and CCR5 Delta 32) have been shown to be associated with renal allograft rejection. The aim of this study was to investigate the association of these polymorphisms with allograft rejection among Pakistani transplant patients. Method: A total of 606 renal transplant patients and an equal number of their donors were included in this study. DNA samples were used to amplify polymorphic regions of CCR2V64I, CCR5-59029G>A and CCR5 Delta 32 by polymerase chain reaction using sequence specific primers. The amplified products of CCRV64I and CCR5-59029G>A were digested with restriction enzymes (BsaB1 and Bsp12861) respectively. The CCR5 Delta 32 genotypes were determined by sizing the PCR amplicons. The association of these polymorphisms with the biopsy proven rejection and other clinical parameters was evaluated using the statistical software SPSS v.17. Results: In this study, the G/G genotype of CCR2V64I was associated with a high frequency of allograft rejection (p=0.009; OR=2.14; 95% CI = 12-3.7). Rejection episode(s) in the GA + AA genotypes were found to be significantly lower as compared to the GG genotype (p=0.009: OR=0.4; 95% CI = 0.2-0.8). The Kaplan-Meier curve also indicated a reduced overall allograft survival for patients with the G/G genotype of CCR2V64I (59.2 +/- 1.4 weeks, log p = 0.008). There was a significant association with rejection by female donors possessing the CCR2 GG genotype (p = 0.02; OR=2.6; CI=1.1-63) and male donors with the CCR5-59029 GG genotype (p=0.004; OR = 1.7; CI=1.03-3.01). Conclusion: This study shows an association of the CCR2V64I (G/G) genotype with renal allograft rejection. However, no such association was found for the CCR5 gene polymorphisms. Therapeutic interventions such as blocking the CCR2 receptor (especially G polymorphism) may yield better survival of renal allograft in this patient group. Further, chemokine receptors may be added to the spectrum of the immunogenetic factors that are known to be associated with renal allograft rejection. (C) 2012 Elsevier B.V. All rights reserved.