title: Genetic variability of major inflammatory mediators has no impact on the outcome of kidney transplantation.
abstract: BACKGROUND
  Functionally relevant polymorphisms in genes of the Th1 and Th2-inflammatory pathway influence the susceptibility to acute rejection (AR), chronic allograft nephropathy (CAN), and subclinical rejection (SR) as well as graft survival after renal transplantation. Because these findings have not been validated, we sought confirmatory evidence of these associations in a larger group of renal transplant recipients.
  
  
  METHODS
  A total of 436 kidney transplant recipients were genotyped for 9 single nucleotide polymorphisms (TNF-alpha-308G/A, MCP-1-2518A/G, RANTES-403G/A, -109T/C and -28C/G, CCR2+190G/A, IFN-gamma+874A/T, TGF-beta+869T/C and +915G/C) and for the 32-bp indel polymorphism in CCR5. The effects of these polymorphisms on the incidence of AR, SR, CAN and graft survival were analyzed in single locus and haplotype models.
  
  
  RESULTS
  Single locus analysis revealed that there was no significant difference in the distribution of the genotype frequencies between patients with and without AR, and between patients with CAN or SR, and individuals without CAN. Furthermore, no influence of any of the polymorphisms on the long-term graft survival was observed. Haplotype [TGF-beta +869G; TGF-beta +915C] seemed to be associated with the presence of SR (odds ratio: 3.45, 95% confidence interval: 1.19 - 9.99, P=0.023), but the association was nonsignificant due to the insufficient power.
  
  
  CONCLUSIONS
  In contrast to previous allelic association studies, neither of the polymorphisms has been associated with the outcome of kidney transplantation in the single locus analysis nor in the haplotype model. Our findings reinforce the need for more rigorous research compliant with the currently accepted standards for polymorphism-disease association studies.
authors.affiliation: Transplant Laboratory, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Irena
authors.initials: I
authors.lastname: Brabcova
authors.forename: Jan
authors.initials: J
authors.lastname: Petrasek
authors.forename: Petra
authors.initials: P
authors.lastname: Hribova
authors.forename: Katerina
authors.initials: K
authors.lastname: Hyklova
authors.forename: Katerina
authors.initials: K
authors.lastname: Bartosova
authors.forename: Jiri
authors.initials: J
authors.lastname: Lacha
authors.forename: Ondrej
authors.initials: O
authors.lastname: Viklický
mesh_terms: D000328:Adult; D000368:Aged; D016207:Cytokines / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006084:Graft Rejection / Q000235:genetics*; D006085:Graft Survival / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000235:genetics; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis
chemical_list: D016207:Cytokines