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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
|
| pubmed:dateCreated |
1997-5-2
|
| pubmed:abstractText |
Tumor necrosis factor (TNF) is recognized as a central mediator of sepsis, septic shock, and multiple organ failure. These host reactions are associated with increased TNF levels in circulation, presumably due to increased TNF production. A previously described nucleotide variation at position -308 in the promoter region of the human TNF gene was shown to be associated with the clinical outcome of malaria. In this study we addressed the relevance of the -308 polymorphism for expression of the human TNF gene in response to bacterial endo- toxin in vivo and in vitro. First, we typed 80 patients suffering from severe sepsis and 153 healthy individuals and found no association of the -308 variation with incidence of the disease. In contrast, the NcoI marker in the closely linked lymphotoxin-alpha (LT-alpha) gene showed association with survivaL This discrepancy can be explained by the linkage of the TNFB2(NcoI) allele to the common TNF1 (-308) allele. Second, we generated reporter gene constructs with the promoter deletions and with both -308 variation in the context of the extended human TNF promoter region. Although such constructs were highly inducible by lipopolysaccharide (LPS) in transient transfections into a macrophage cell line, the -308 variation had no significant effect on transcription, consistent with the promoter deletion study. We conclude that the functional consequence of the -308 polymorphism may be unrelated to transcriptional response of the TNF gene to bacterial endotoxin.
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| pubmed:commentsCorrections | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Deoxyribonucleases, Type II...,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/endodeoxyribonuclease NcoI
|
| pubmed:status |
MEDLINE
|
| pubmed:issn |
1078-7852
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
46
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
42-50
|
| pubmed:dateRevised |
2008-11-21
|
| pubmed:meshHeading |
pubmed-meshheading:8832971-Adult,
pubmed-meshheading:8832971-Aged,
pubmed-meshheading:8832971-Alleles,
pubmed-meshheading:8832971-Animals,
pubmed-meshheading:8832971-Cell Line,
pubmed-meshheading:8832971-Deoxyribonucleases, Type II Site-Specific,
pubmed-meshheading:8832971-Gene Deletion,
pubmed-meshheading:8832971-Heterozygote,
pubmed-meshheading:8832971-Homozygote,
pubmed-meshheading:8832971-Humans,
pubmed-meshheading:8832971-Lipopolysaccharides,
pubmed-meshheading:8832971-Mice,
pubmed-meshheading:8832971-Middle Aged,
pubmed-meshheading:8832971-Mutagenesis, Site-Directed,
pubmed-meshheading:8832971-Polymorphism, Genetic,
pubmed-meshheading:8832971-Promoter Regions, Genetic,
pubmed-meshheading:8832971-Sepsis,
pubmed-meshheading:8832971-Survival Rate,
pubmed-meshheading:8832971-Tumor Necrosis Factor-alpha
|
| pubmed:articleTitle |
-308 tumor necrosis factor (TNF) polymorphism is not associated with survival in severe sepsis and is unrelated to lipopolysaccharide inducibility of the human TNF promoter.
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| pubmed:affiliation |
Clinic for Anesthesiology and Intensive Care Medicine, Christian-Albrechts-University, Kiel, Germany.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|