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Transplantation. 2002 Jun 27;73(12):1886-91.

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

Author information

  • 1Department of Pathology and Laboratory Medicine, UMDNJ-New Jersey Medical School, Newark, New Jersey 07103, USA. fernande@umdnj.edu

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.

PMID:
12131682
[PubMed - indexed for MEDLINE]
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