title: 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) Delta 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 CCR5Delta32.
  
  
  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.
authors: Department of Internal Medicine, Seoul National University College of Medicine, Korea.
authors: Ran-hui
authors: RH
authors: Cha
authors: Seung Hee
authors: SH
authors: Yang
authors: Hyo Sang
authors: HS
authors: Kim
authors: Sun Moon
authors: SM
authors: Kim
authors: Myoung Hee
authors: MH
authors: Park
authors: Jongwon
authors: J
authors: Ha
authors: Yon Su
authors: YS
authors: Kim
mesh_terms: D000208:Acute Disease; D000328:Adult; D000483:Alleles; D001483:Base Sequence; D003404:Creatinine / Q000097:blood; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D006085:Graft Survival / Q000235:genetics / Q000276:immunology; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology* / Q000502:physiology; D007723:Korea; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019713:Receptors, CCR5 / Q000235:genetics*; D017384:Sequence Deletion; D013997:Time Factors; D014019:Tissue Donors; D055815:Young Adult
chemical_list: D017931:DNA Primers; D019713:Receptors, CCR5; D003404:Creatinine