Investigation of promoter polymorphisms in the tumor necrosis factor-alpha and interleukin-10 genes in liver transplant patients

Transplantation. 2002 Jun 27;73(12):1886-91. doi: 10.1097/00007890-200206270-00006.


Background: Cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 play significant roles in the inflammatory and immune responses that mediate allograft rejection. The presence of a G-->A polymorphism at position -308 in the promoter region of the TNF-alpha gene increased its transcription 6- to 7-fold. A similar polymorphism at position -1082 of the IL-10 promoter results in decreased production of IL-10 protein. In this study we have determined whether the single nucleotide polymorphisms in the promoter regions of the TNF-alpha and IL-10 genes can predict the outcome of the allograft in liver recipients.

Methods: DNA was extracted from whole blood of liver recipients. The genotype of the patients was determined by polymerase chain reaction using sequence-specific primers. The level of TNF-alpha and IL-10 protein was measured by ELISA after stimulation of peripheral blood mononuclear cells with concanavalin A.

Results: There was significant correlation between acute cellular rejection and the presence of the -308A polymorphism (P<0.001), with 8 of 13 patients with the TNF-alpha polymorphism having evidence of acute rejection. Cell stimulation studies revealed that the level of TNF-alpha protein produced by patients with liver rejection was significantly higher than for patients without rejection (P=0.001). There were no strong associations between the presence of the IL-10 polymorphisms and rejection (P=0.71).

Conclusions: This study adds to the understanding of the role of cytokine polymorphisms in liver transplants. The data suggest that cytokine promoter polymorphisms may be a risk factor associated with allograft rejection in the liver.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Genotype
  • Graft Rejection
  • Humans
  • Interleukin-10 / genetics*
  • Liver Transplantation*
  • Middle Aged
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic*
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / genetics*


  • Tumor Necrosis Factor-alpha
  • Interleukin-10