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Rapid Genotyping for Tumor Necrosis Factor-[Alpha] (Tnf-[Alpha]) -863C/A Promoter Polymorphism That Determines Tnf-[Alpha] Response (Technical Briefs)

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eBook details

  • Title: Rapid Genotyping for Tumor Necrosis Factor-[Alpha] (Tnf-[Alpha]) -863C/A Promoter Polymorphism That Determines Tnf-[Alpha] Response (Technical Briefs)
  • Author : Clinical Chemistry
  • Release Date : January 01, 2004
  • Genre: Chemistry,Books,Science & Nature,
  • Pages : * pages
  • Size : 200 KB

Description

Tumor necrosis Factor-[alpha] (TNF-[alpha]) plays a central role in orchestrating the inflammatory response (1). Accordingly, blocking TNF-[alpha] activity has become a standard treatment of several inflammatory diseases (2,3). TNF-[alpha] production shows high interindividual variations, which have been assigned mainly to inherited factors (4). Several genetic polymorphisms related to TNF-[alpha] synthesis have been detected in the TNF gene (5, 6). The -308 promoter polymorphism was found to affect TNF-[alpha] production by some authors (7) but not by others (8). Similar inconsistencies have been found for the association of this polymorphic site with susceptibility to and/or outcome of sepsis (8,9). The Ncol polymorphism located within the first intron of the lymphotoxin A (LTA) gene was reported to be associated with TNF-[alpha] plasma concentrations (8). In a recent report, de Jong et al. (10) found no relationship between ex vivo TNF-[alpha] production on endotoxin stimulation of human whole blood and +489, -238, and -376 single-nucleotide polymorphisms or TNFa microsatellites of the TNF-[alpha] gene (10). Thus, the genetic factors determining the TNF-[alpha] response to infection are still poorly defined. Recently, Skoog et al. (11) identified a C/A exchange at position -863 of the TNF-[alpha] gene promoter and found higher transcriptional activity of the C allele in reporter gene assays. This polymorphic site was found to be associated with thyroid-associated ophthalmopathy (12), Crohn disease (13), juvenile rheumatoid arthritis (14), and the lumbar spine area (15).


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