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

Helen Fernandes, Baburao Koneru, Neil Fernandes, Meera Hameed, Marion C. Cohen, Elizabeth Raveche, Stanley Cohen

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57 Scopus citations


Background. Cytokines such as tumor necrosis factor (TNF)-α 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-α 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-α 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-α 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-α polymorphism having evidence of acute rejection. Cell stimulation studies revealed that the level of TNF-α 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.

Original languageEnglish (US)
Pages (from-to)1886-1891
Number of pages6
Issue number12
StatePublished - Jun 27 2002

All Science Journal Classification (ASJC) codes

  • Transplantation


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