Genetic interactions between the donor and the recipient for susceptibility to acute rejection in kidney transplantation: polymorphisms of CCR5

Abstract

Background. Acute rejection (AR) contributes to the development of chronic allograft nephropathy that is the major cause of graft failure. We analyzed the 59029G>A polymorphism and an internal 32 bp deletion (CCR5 32) of CCR chemokine receptor 5 (CCR5) and tried to prove the hypothesis that genetic interactions between the donor and the recipient influence the development of AR. Methods. We detected genetic polymorphisms by the TaqMan (R) method and by sizing PCR amplicons (n = 486). The primary outcomes were early acute rejection (EAR) and repeated early acute rejection (RR). We defined EAR as the occurrence of a biopsy-proven AR within 3 months after transplantation. Results. The development of EAR was dependent on the number of A alleles in recipients and showed a dose-response relationship (P = 0.002). When we combined the number of A alleles in both donor and recipient, episodes of EAR and RR were more prevalent as the allelic number increased (A allelic number 0 & 1, 2 versus 3 & 4, P = 0.048; 0 & 1 versus 3 & 4, P = 0.006). Statistical significance was preserved after multivariate analysis of sex, HLA mismatch and type of donor with the recipient`s age as the continuous term. Also, graft survival was different according to the presence of the A allele, i.e. recipients carrying A allele (+) grafts showed poor graft survival (P = 0.008 by a log-rank test). Again, the number of A alleles affected graft survival as the recipients who carried more A alleles had poor graft survival (A allele number 0 & 1 versus 2 versus 3 & 4, P = 0.011; 0 & 1 versus 3 & 4, P = 0.08; 0 & 1 versus 2, P = 0.002; by a log-rank test). All of the participants were wild-type homozygotes for CCR5 delta 32. Conclusions. The A allele of CCR5 59029G > A was a risk factor for EAR and RR. As the number of A alleles increased, episodes of EAR were more frequently observed.This study was supported by a grant from the Korea Health 21 R & D project, Ministry of Health and Welfare, Republic of Korea (03-PJ10-PG13-GD01-0002).Thio CL, 2008, J IMMUNOL, V181, P7944Wang F, 2008, SCHIZOPHR RES, V101, P341, DOI 10.1016/j.schres.2008.01.015Berce V, 2008, J ASTHMA, V45, P780, DOI 10.1080/02770900802386024Takacova M, 2008, ACTA VIROL, V52, P261Yigit B, 2007, CELL BIOCHEM FUNCT, V25, P423, DOI 10.1027/cbf.1322Ahn SH, 2006, J MED VIROL, V78, P1564, DOI 10.1002/jmv.20739Prahalad S, 2006, GENES IMMUN, V7, P468, DOI 10.1038/sj.gene.6364317Nankivell BJ, 2006, TRANSPLANTATION, V81, P643, DOI 10.1097/01.tp.0000190423.82154.01Marin LA, 2006, TISSUE ANTIGENS, V67, P117, DOI 10.1111/j.1399-0039.2005.00538.xSimeoni E, 2005, TRANSPLANTATION, V80, P1309, DOI 10.1097/01.tp.0000178378.53616.caLacha J, 2005, TRANSPLANT P, V37, P764, DOI 10.1016/j.transproceed.2004.12.224ABUL KA, 2005, CELLULAR MOL IMMUNOL, P375Hoffmann S, 2004, KIDNEY INT, V66, P1686Fernandez-Mestre MT, 2004, HUM IMMUNOL, V65, P725, DOI 10.1016/j.humimm.2004.05.002Ruster M, 2004, CLIN NEPHROL, V61, P30CLARK VJ, 2004, HUM GENOMICS, V1, P255Nakajima K, 2003, DIABETES CARE, V26, P892Schroppel B, 2002, J CLIN IMMUNOL, V22, P381El-Sawy T, 2002, CURR OPIN IMMUNOL, V14, P562Keen LJ, 2002, TRANSPL IMMUNOL, V10, P143Inston NG, 2002, NEPHROL DIAL TRANSPL, V17, P1374Abdi R, 2002, J AM SOC NEPHROL, V13Fischereder M, 2001, LANCET, V357, P1758Hancock WW, 2001, J EXP MED, V193, P975Hancock WW, 2000, CURR OPIN IMMUNOL, V12, P511Grone HJ, 1999, FASEB J, V13, P1371Schlondorff D, 1997, KIDNEY INT, V51, P610Naruse K, 1996, GENOMICS, V34, P236