Cytokine Gene Polymorphisms in Kidney Transplantation

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. Objectives. We sought to investigate polymorphisms of tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta 1, interleukin (IL)-10, IL-6, and interferon (IFN)-gamma as indices of differential cytokine production in kidney transplantation and to examine their predictive roles for acute or chronic rejection. Patients and Methods. TNF-alpha (G/A -308), TGF -beta 1 (haplotype codon 10/codon 25), IL-10 (haplotype-1082, -819, -592), IL-6 (C/G -174), and IFN-gamma (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-beta 1 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-alpha*H/TGF- beta 1*H/IL-10*H production haplotype (75%) compared with the other haplotypes (16%; P = .03). Conclusion. The presence of TGF-beta 1-H secretion profile may protect the kidney graft. TNF-alpha*H/TGF-beta 1*H/IL-10*H haplotype was associated with a higher risk of ARE and with poorer graft survival.