Genetic interactions between the donor and the recipient for susceptibility to acute rejection in kidney transplantation: polymorphisms of CCR5.
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.
Cha
Ran-hui
RH
Department of Internal Medicine, Seoul National University College of Medicine, Korea.
Yang
Seung Hee
SH
Kim
Hyo Sang
HS
Kim
Sun Moon
SM
Park
Myoung Hee
MH
Ha
Jongwon
J
Kim
Yon Su
YS
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
D017931:DNA Primers; D019713:Receptors, CCR5; D003404:Creatinine