title: The effect of cytokine gene polymorphisms on pediatric heart allograft outcome.
abstract: BACKGROUND
  Cytokines play a major role in the inflammatory and immune responses that mediate allograft outcome. Several studies have shown that the production of cytokines varies among individuals and these variations are determined by genetic polymorphisms, most commonly within the regulatory region of the cytokine gene. The aim of this study was to assess the effect of these allelic variations on acute rejection after pediatric heart transplantation.
  
  
  METHODS
  We performed cytokine genotyping using polymerase chain reaction-sequence specific primers in 93 pediatric heart transplant recipients and 29 heart donors for the following functional polymorphisms: tumor necrosis factor-alpha (TNF-alpha) (-308), interleukin (IL)-10 (-1082, -819, and -592), TGF-beta1 (codon 10 and 25), IL-6 (-174), and interferon-gamma (INF-gamma) (+874). The distribution of polymorphisms in this population did not differ from published controls. The patients were classified as either non-rejecters (0 or 1 episode) or rejecters (> 1 episode) based on the number of biopsy proven rejection episodes in the first year after transplantation.
  
  
  RESULTS
  Forty-two of the 69 TNF-alpha patients (61%) in the low producer group were non-rejecters, while 9 of the 24 (37.5%) with high TNF-alpha were non-rejecters (p = 0.047). In contrast, IL-10 genotype showed the opposite finding. Forty-two of the 66 patients (64%) in the high and intermediate IL-10 group were non-rejecters, while 9 of the 26 (35%) in the low IL-10 group were non-rejecters (p = 0.011). The combination of low TNF-alpha with a high or intermediate IL-10 genotype was associated with the lowest risk of rejection (34/49 or 69% non-rejecters). Neither the distribution of the IL-6, INF-gamma, and TGF-beta1 genotype in recipients nor the donor genotype showed any association with acute rejection.
  
  
  CONCLUSIONS
  Genetic polymorphisms that have been associated with low TNF-alpha and high IL-10 production are associated with a lower number of acute rejection episodes after pediatric heart transplantation.
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Thomas E. Starzl Transplant Institute and Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA. mrawad+@pitt.edu
authors.forename: M R
authors.initials: MR
authors.lastname: Awad
authors.forename: S
authors.initials: S
authors.lastname: Webber
authors.forename: G
authors.initials: G
authors.lastname: Boyle
authors.forename: C
authors.initials: C
authors.lastname: Sturchioĉ
authors.forename: M
authors.initials: M
authors.lastname: Ahmed
authors.forename: J
authors.initials: J
authors.lastname: Martell
authors.forename: Y
authors.initials: Y
authors.lastname: Law
authors.forename: S A
authors.initials: SA
authors.lastname: Miller
authors.forename: P
authors.initials: P
authors.lastname: Bowman
authors.forename: S
authors.initials: S
authors.lastname: Gribar
authors.forename: F
authors.initials: F
authors.lastname: Pigula
authors.forename: G
authors.initials: G
authors.lastname: Mazariegos
authors.forename: B P
authors.initials: BP
authors.lastname: Griffith
authors.forename: A
authors.initials: A
authors.lastname: Zeevi
mesh_terms: D000293:Adolescent; D002648:Child; D016207:Cytokines / Q000235:genetics*; D006084:Graft Rejection / Q000235:genetics*; D006085:Graft Survival / Q000235:genetics; D016027:Heart Transplantation; D006801:Humans; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis
chemical_list: D016207:Cytokines