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, CCR5D32, and SDF1-3ƒA polymorphisms, and examined their association on outcomes in liver allograft recipients. Due to the low number of patients homozygous for CCR2-64I and CCR5D32, 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 SDF1-3ƒA allele was significantly (p Ω0.034) higher in patients who died (29.0%, n Ω 31) compared to recipients still alive (17.1%, n Ω 172). The mean patient survival time post transplant was 134 months in patients with SDF1 wild-type, significantly (log rank p Ω0.014) longer than 98 months in patients with at least one SDF1-3ƒA allele. The CCR2 and CCR5 polymorphisms were not associated with significant differences in mortality rate. In conclusion, CCR2-64I, CCR5D32, and SDF1-3ƒA genotypes did not influence the risk for acute rejection or graft survival. However, in liver allograft recipients SDF1-3ƒA is significantly associated with higher mortality.

A Monocyte Chemoattractant Protein-1 (MCP-1) Polymorphism And Outcome After Renal Transplantation

“…This is in accordance with our previous observation that CCR2-64I was not associated with acute rejection or graft survival in 207 liver transplant recipients (24). Our data contrast however with a recent study where the heterozygous CCR2-64I variant was associated with decreased incidence of acute rejection (P ϭ 0.014) in 163 kidney transplant recipients.…”

Polymorphisms in CCL2&CCL5 chemokines/chemokine receptors genes and their association with diseases

“…CCR5Δ32 is a risk factor for the development of ischemictype biliary lesions after liver transplantation and leads to the reduction in 5-year survival 139 . This relationship between CCR5Δ32 and liver graft survival or risk for liver acute rejection was not reported in previous study 68 .…”

“…CCR2V64I mutation had no effect on kidney, liver or heart graft failure 38,68,69 . However a significant reduction in the risk of acute renal transplant rejection was found in recipients who possessed the CCR2-64I allele 70 .…”

The Impact of Costimulatory Molecule Gene Polymorphisms on Clinical Outcomes in Liver Transplantation

“…Significant associations in particular have been found in cytokine polymorphisms, such as the effect of promoter SNPs TNFa (À 308 G/A) and IL-10 (À 1082 G/A) on gene transcription (23,24), cytokine production (25,26), and incidence of acute rejection in liver (27) and other solid organ transplants (28)(29)(30)(31). Furthermore, polymorphisms in chemokine SDF1 (3 0 A) and chemokine receptor CCR5 (D32) have been noted to have associations in clinical outcomes of liver and kidney transplantation (32,33).…”