Investigation of promoter polymorphisms in the tumor necrosis factor-alpha and interleukin-10 genes in liver transplant patients. Academic Article uri icon

Overview

abstract

  • 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.

publication date

  • June 27, 2002

Research

keywords

  • Interleukin-10
  • Liver Transplantation
  • Polymorphism, Genetic
  • Promoter Regions, Genetic
  • Tumor Necrosis Factor-alpha

Identity

Scopus Document Identifier

  • 0037182838

Digital Object Identifier (DOI)

  • 10.1097/00007890-200206270-00006

PubMed ID

  • 12131682

Additional Document Info

volume

  • 73

issue

  • 12