title: Interferon-γ +874 polymorphism in the first intron of the human interferon-γ gene and kidney allograft outcome.
abstract: BACKGROUND
  Despite advances in immunosuppressive therapy in the past decade, allograft rejection remains an important cause of kidney graft failure. Cytokines play a major role in the inflammatory and immune responses that mediate allograft outcomes. Several studies have shown that the production of cytokines varies among individuals. These variations are determined by genetic polymorphisms, most commonly within the regulatory region of cytokine genes. The aim of the present study was to assess the effect of allelic variation on acute rejection episodes (ARE) or chronic allograft nephropathy (CAN) after kidney transplantation.
  
  
  METHODS
  To determine a possible correlation between the interferon (INF)-γ +874 polymorphism and kidney allograft outcome, we isolated genomic DNA from 74 patients who underwent isolated kidney allografts and were classified into 2 groups--a rejection and a nonrejection group--for comparison with a control group of 163 healthy subjects.
  
  
  RESULTS
  We genotyped INF-γ +874 polymorphisms in all groups. The transplant group showed a significantly increased homozygous genotype T/T (P = .0118) compared with healthy controls. Similarly, considering only patients with CAN, the homozygous genotype T/T (P = .0067) was significantly increased compared with the healthy controls. The rejection group indicated a significant increased homozygous genotype T/T compared with the control group (P = .0061).
  
  
  CONCLUSIONS
  Homozygous genotype T/T was associated with increased levels of INF-γ and greater numbers among the rejection and CAN cohorts.
authors.affiliation: Department of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil. janacrispim@usp.br
authors.forename: J C O
authors.initials: JC
authors.lastname: Crispim
authors.forename: I J
authors.initials: IJ
authors.lastname: Wastowski
authors.forename: D M
authors.initials: DM
authors.lastname: Rassi
authors.forename: C T
authors.initials: CT
authors.lastname: Mendes-Junior Silva
authors.forename: C
authors.initials: C
authors.lastname: Bassi
authors.forename: E C
authors.initials: EC
authors.lastname: Castelli
authors.forename: R S
authors.initials: RS
authors.lastname: Costa
authors.forename: L T
authors.initials: LT
authors.lastname: Saber
authors.forename: T G A
authors.initials: TG
authors.lastname: Silva
authors.forename: E A
authors.initials: EA
authors.lastname: Donadi
mesh_terms: D001706:Biopsy; D016022:Case-Control Studies; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics*; D007438:Introns; D016030:Kidney Transplantation; D011110:Polymorphism, Genetic; D014184:Transplantation, Homologous
chemical_list: D007371:Interferon-gamma