The Impact of Polymorphisms in Chemokine and Chemokine Receptors on Outcomes in Liver Transplantation

Abstract

Chemokines and their corresponding receptors likely play a central role in directing mononuclear cells to the graft sites during rejection. Genes for the chemokine stromal derived factor-1 (SDF1) and CC chemokine receptors CCR2 and CCR5 are characterized by polymorphisms which alter their function. We genotyped DNA of 207 liver transplant recipients by PCR or PCR-RFLP for CCR2-641, CCR5delta32, and SDF1-3'A polymorphisms, and examined their association on outcomes in liver allograft recipients. Due to the low number of patients homozygous for CCR2-641 and CCR5delta32, only the effects of their heterozygous variants were addressed in this study. None of the investigated polymorphisms showed a significant shift in gene frequency in acute rejection and rejection-free groups, or for graft survival. The gene frequency of the SDF1-3'A allele was significantly (p = 0.034) higher in patients who died (29.0%, n = 31) compared to recipients still alive (17.1%, n = 172). The mean patient survival time post transplant was 134 months in patients with SDF1 wild-type, significantly (log rank p = 0.014) longer than 98 months in patients with at least one SDF1-3'A allele. The CCR2 and CCR5 polymorphisms were not associated with significant differences in mortality rate. In conclusion, CCR2-641, CCR5delta32, and SDF1-3'A genotypes did not influence the risk for acute rejection or graft survival. However, in liver allograft recipients SDF1-3'A is significantly associated with higher mortality.