Mortality in adult intensive care patients with severe systemic inflammatory response syndromes is strongly associated with the hypo-immune TNF-238A polymorphism

Pappachan, John V., Coulson, Tim G., Child, Nicholas J. A., Markham, David J., Nour, Sarah M., Pulletz, Mark C. K., Rose-Zerilli, Matthew J., de Courcey-Golder, Kim, Barton, Sheila J., Yang, Ian A. and Holloway, John W. (2009) Mortality in adult intensive care patients with severe systemic inflammatory response syndromes is strongly associated with the hypo-immune TNF-238A polymorphism. Immunogenetics, 61 10: 657-662. doi:10.1007/s00251-009-0395-6


Author Pappachan, John V.
Coulson, Tim G.
Child, Nicholas J. A.
Markham, David J.
Nour, Sarah M.
Pulletz, Mark C. K.
Rose-Zerilli, Matthew J.
de Courcey-Golder, Kim
Barton, Sheila J.
Yang, Ian A.
Holloway, John W.
Title Mortality in adult intensive care patients with severe systemic inflammatory response syndromes is strongly associated with the hypo-immune TNF-238A polymorphism
Formatted title
Mortality in adult intensive care patients with severe systemic inflammatory response syndromes is strongly associated with the hypo-immune TNF-238A polymorphism
Journal name Immunogenetics   Check publisher's open access policy
ISSN 0093-7711
1432-1211
Publication date 2009-10
Sub-type Article (original research)
DOI 10.1007/s00251-009-0395-6
Volume 61
Issue 10
Start page 657
End page 662
Total pages 6
Place of publication Heidelberg, Germany
Publisher Springer
Language eng
Formatted abstract
The systemic inflammatory response syndrome (SIRS) is associated with activation of innate immunity. We studied the association between mortality and measures of disease severity in the intensive care unit (ICU) and functional polymorphisms in genes coding for Toll-like receptor 4 (TLR4), macrophage migratory inhibitory factor (MIF), tumour necrosis factor (TNF) and lymphotoxin-alpha (LTA). Two hundred thirty-three patients with severe SIRS were recruited from one general adult ICU in a tertiary centre in the UK. DNA from patients underwent genotyping by 5′ nuclease assay. Genotype was compared to phenotype. Primary outcome was mortality in ICU. Minor allele frequencies were TLR4 +896G 7%, MIF 173C 16%, TNF −238A 10% and LTA +252G 34%. The frequency of the hypoimmune minor allele TNF −238A was significantly higher in patients who died in ICU compared to those who survived (p = 0.0063) as was the frequency of the two haplotypes LTA +252G, TNF −1031T, TNF −308G, TNF −238A and LTA +252G, TNF−1031T, TNF−308A and TNF−238A (p = 0.0120 and 0.0098, respectively). These findings re-enforce the view that a balanced inflammatory/anti-inflammatory response is the most important determinant of outcome in sepsis. Genotypes that either favour inflammation or its counter-regulatory anti-inflammatory response are likely to influence mortality and morbidity.
Keyword Systemic inflammatory response syndrome
Toll-like receptor 4
Macrophage migration inhibitory factor
Polymorphism (genetics)
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Tue, 01 Mar 2011, 12:16:51 EST