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 CCR2–64I, CCR5Δ32, and SDF1–3′A polymorphisms, and examined their association on outcomes in liver allograft recipients. Due to the low number of patients homozygous for CCR2–64I and CCR5Δ32, 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, CCR2–64I, CCR5Δ32, 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.