The impact of polymorphisms in chemokine and chemokine receptors on outcomes in liver transplantation.
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.
Division of Nephrology Mount Sinai School of Medicine, New York, NY, USA. bernd.schroppel@mssm.edu
Bernd
B
Schröppel
Michael
M
Fischereder
Rami
R
Ashkar
Marvin
M
Lin
Bernhard K
BK
Krämer
Brad
B
Mardera
Tom
T
Schiano
Barbara
B
Murphy
D054377:Chemokine CXCL12; D018925:Chemokines / Q000235:genetics*; D019743:Chemokines, CXC / Q000235:genetics; D005006:Ethnicity; D005260:Female; D005838:Genotype; D006084:Graft Rejection / Q000453:epidemiology; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D016031:Liver Transplantation / Q000276:immunology / Q000401:mortality / Q000502:physiology*; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D019713:Receptors, CCR5 / Q000235:genetics; D019707:Receptors, Chemokine / Q000235:genetics*; D012189:Retrospective Studies; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D018925:Chemokines; D019743:Chemokines, CXC; D019713:Receptors, CCR5; D019707:Receptors, Chemokine