title: Cytokine gene polymorphisms in kidney transplantation.
abstract: BACKGROUND
  Acute and chronic rejections remain an important cause of graft loss after renal transplantation. It has been suggested that cytokine genotyping may have a predictive role to identify patients at greater risk of rejection regardless of human leukocyte antigen (HLA) compatibility and/or the presence of anti-HLA antibodies before the renal allograft.
  
  
  OBJECTIVE
  We sought to investigate polymorphisms of tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1, interleukin (IL)-10, IL-6, and interferon (IFN)-γ as indices of differential cytokine production in kidney transplantation and to examine their predictive roles for acute or chronic rejection.
  
  
  METHODS
  TNF-α (G/A -308), TGF -β1 (haplotype codon 10/codon 25), IL-10 (haplotype-1082, -819, -592), IL-6 (C/G -174), and IFN-γ (T/A +874) single nucleotide polymorphisms (SNPs) were detected using polymerase chain reaction (PCR)-specific sequence primers (SSP) in 231 kidney transplant recipients (KTR) including 106 treated with mycophenolate mofetil (MMF+).
  
  
  RESULTS
  We observed no significant associations of any of investigated polymorphism taken alone with acute rejection episodes (ARE) or chronic allograft dysfunction (CAD). Nevertheless, TGF-β1 Low (L) production was correlated with greater graft survival at 20 years (81.8%) compared with intermediate (L) or high (H) levels (56.1%), affect that the difference was not significant (P = .2). Cytokine haplotype analysis in KTR (MMF-) without HLA-mismatches or presynthesized anti-HLA antibodies (n = 32) showed ARE to be significantly more prevalent among the TNF-α*H/TGF- β1*H/IL-10*H production haplotype (75%) compared with the other haplotypes (16%; P = .03).
  
  
  CONCLUSIONS
  The presence of TGF-β1-H secretion profile may protect the kidney graft. TNF-α*H/TGF-β1*H/IL-10*H haplotype was associated with a higher risk of ARE and with poorer graft survival.
authors.affiliation: Laboratory of Research in Immunology of Renal Transplantation and Immunopathology (LR03SP01), University Tunis EI Manar, Charles Nicolle Hospital, Tunis, Tunisia. dhaouaditarak@yahoo.fr
authors.forename: T
authors.initials: T
authors.lastname: Dhaouadi
authors.forename: I
authors.initials: I
authors.lastname: Sfar
authors.forename: R
authors.initials: R
authors.lastname: Bardi
authors.forename: S
authors.initials: S
authors.lastname: Jendoubi-Ayed
authors.forename: T B
authors.initials: TB
authors.lastname: Abdallah
authors.forename: K
authors.initials: K
authors.lastname: Ayed
authors.forename: Y
authors.initials: Y
authors.lastname: Gorgi
mesh_terms: D000208:Acute Disease; D002908:Chronic Disease; D016207:Cytokines / Q000097:blood / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006084:Graft Rejection / Q000097:blood / Q000235:genetics* / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D016207:Cytokines; C573415:IFNG protein, human; C508609:IL10 protein, human; C508600:IL6 protein, human; D007166:Immunosuppressive Agents; D015850:Interleukin-6; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma