The University of Southampton
University of Southampton Institutional Repository

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
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.
f5322de3-0d81-4ab6-9526-d291d88c335b
Coulson, T.G.
2a728c3e-657f-4ac1-975a-2dfbd6885719
Child, N.J.A.
d08786f6-578e-4ab2-95be-f2b00ed89da7
Markham, D.J.
0ec8231d-040b-44a5-b638-e48732f9333c
Nour, S.M.
6d2669cf-62cf-4dca-883e-c36020c162ae
Pulletz, M.C.K.
c22cbb39-22b5-4c4c-bd4a-0b048aa117fa
Rose-Zerilli, M.J.
08b3afa4-dbc2-4c0d-a852-2a9f33431199
de Courcey-Golder, K.
5e4f66d1-733c-471b-9451-7a286cc7acc0
Barton, S.J.
4f674382-ca0b-44ad-9670-e71a0b134ef0
Yang, I.A.
0da6e2cb-d200-440e-ba70-48fb8e7738cd
Holloway, J.W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Pappachan, J.V.
f5322de3-0d81-4ab6-9526-d291d88c335b
Coulson, T.G.
2a728c3e-657f-4ac1-975a-2dfbd6885719
Child, N.J.A.
d08786f6-578e-4ab2-95be-f2b00ed89da7
Markham, D.J.
0ec8231d-040b-44a5-b638-e48732f9333c
Nour, S.M.
6d2669cf-62cf-4dca-883e-c36020c162ae
Pulletz, M.C.K.
c22cbb39-22b5-4c4c-bd4a-0b048aa117fa
Rose-Zerilli, M.J.
08b3afa4-dbc2-4c0d-a852-2a9f33431199
de Courcey-Golder, K.
5e4f66d1-733c-471b-9451-7a286cc7acc0
Barton, S.J.
4f674382-ca0b-44ad-9670-e71a0b134ef0
Yang, I.A.
0da6e2cb-d200-440e-ba70-48fb8e7738cd
Holloway, J.W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a

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), 657-662. (doi:10.1007/s00251-009-0395-6).

Record type: Article

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.

This record has no associated files available for download.

More information

Published date: October 2009

Identifiers

Local EPrints ID: 69860
URI: http://eprints.soton.ac.uk/id/eprint/69860
PURE UUID: 47095afd-355b-4cce-bf85-8785943e5acb
ORCID for M.J. Rose-Zerilli: ORCID iD orcid.org/0000-0002-1064-5350
ORCID for S.J. Barton: ORCID iD orcid.org/0000-0003-4963-4242
ORCID for J.W. Holloway: ORCID iD orcid.org/0000-0001-9998-0464

Catalogue record

Date deposited: 08 Dec 2009
Last modified: 14 Mar 2024 02:56

Export record

Altmetrics

Contributors

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: S.J. Barton ORCID iD
Author: I.A. Yang
Author: J.W. Holloway ORCID iD

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×