Mortality in adult intensive care patients with severe systemic inflammatory response symdroles is strongly associated with the hypoimmune TNF-238A polymorphism
Mortality in adult intensive care patients with severe systemic inflammatory response symdroles is strongly associated with the hypoimmune TNF-238A polymorphism
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.
657-662
Pappachan, J.V.
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Coulson, T.G.
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Child, N.J.A.
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Markham, D.J.
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Nour, S.M.
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Pulletz, M.C.K.
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Rose-Zerilli, M.J.
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de Courcey-Golder, K.
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Barton, S.J.
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Yang, I.A.
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Holloway, J.W.
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October 2009
Pappachan, J.V.
f5322de3-0d81-4ab6-9526-d291d88c335b
Coulson, T.G.
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Child, N.J.A.
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Markham, D.J.
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Nour, S.M.
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Pulletz, M.C.K.
c22cbb39-22b5-4c4c-bd4a-0b048aa117fa
Rose-Zerilli, M.J.
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de Courcey-Golder, K.
5e4f66d1-733c-471b-9451-7a286cc7acc0
Barton, S.J.
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Yang, I.A.
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Holloway, J.W.
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Pappachan, J.V., Coulson, T.G., Child, N.J.A., Markham, D.J., Nour, S.M., Pulletz, M.C.K., Rose-Zerilli, M.J., de Courcey-Golder, K., Barton, S.J., Yang, I.A. and Holloway, J.W.
(2009)
Mortality in adult intensive care patients with severe systemic inflammatory response symdroles is strongly associated with the hypoimmune TNF-238A polymorphism.
Immunogenetics, 61 (10), .
(doi:10.1007/s00251-009-0395-6).
Abstract
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.
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Published date: October 2009
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Local EPrints ID: 69860
URI: http://eprints.soton.ac.uk/id/eprint/69860
PURE UUID: 47095afd-355b-4cce-bf85-8785943e5acb
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Date deposited: 08 Dec 2009
Last modified: 14 Mar 2024 02:56
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Author:
J.V. Pappachan
Author:
T.G. Coulson
Author:
N.J.A. Child
Author:
D.J. Markham
Author:
S.M. Nour
Author:
M.C.K. Pulletz
Author:
K. de Courcey-Golder
Author:
I.A. Yang
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