TNF and TNFR polymorphisms in severe sepsis and septic shock: a prospective multicentre study.

Tumour necrosis factor (TNF) is an important pro-inflammatory cytokine produced in sepsis. Studies examining the association of individual TNF single nucleotide polymorphisms with sepsis have produced conflicting results. This study investigated whether common polymorphisms of the TNF locus and the...

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Main Authors: Gordon, A, Lagan, A, Aganna, E, Cheung, L, Peters, C, McDermott, M, Millo, J, Welsh, K, Holloway, P, Hitman, G, Piper, R, Garrard, C, Hinds, C
Format: Journal article
Language:English
Published: 2004
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author Gordon, A
Lagan, A
Aganna, E
Cheung, L
Peters, C
McDermott, M
Millo, J
Welsh, K
Holloway, P
Hitman, G
Piper, R
Garrard, C
Hinds, C
author_facet Gordon, A
Lagan, A
Aganna, E
Cheung, L
Peters, C
McDermott, M
Millo, J
Welsh, K
Holloway, P
Hitman, G
Piper, R
Garrard, C
Hinds, C
author_sort Gordon, A
collection OXFORD
description Tumour necrosis factor (TNF) is an important pro-inflammatory cytokine produced in sepsis. Studies examining the association of individual TNF single nucleotide polymorphisms with sepsis have produced conflicting results. This study investigated whether common polymorphisms of the TNF locus and the two receptor genes, TNFRSF1A and TNFRSF1B, influence circulating levels of encoded proteins, and whether individual polymorphisms or extended haplotypes of these genes are associated with susceptibility, severity of illness or outcome in adult patients with severe sepsis or septic shock. A total of 213 Caucasian patients were recruited from eight intensive care units (ICU) in the UK and Australia. Plasma levels of TNF (P = 0.02), sTNFRSF1A (P = 0.005) and sTNFRSF1B (P = 0.01) were significantly higher in those who died on ICU compared to those who survived. There was a positive correlation between increasing soluble receptor levels and organ dysfunction (increasing SOFA score) (sTNFRSF1A R = 0.51, P < 0.001; sTNFRSF1B R = 0.53, P < 0.001), and in particular with the degree of renal dysfunction. In this study, there were no significant associations between the selected candidate TNF or TNF receptor polymorphisms, or their haplotypes, and susceptibility to sepsis, illness severity or outcome. The influence of polymorphisms of the TNF locus on susceptibility to, and outcome from sepsis remains uncertain.
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spelling oxford-uuid:2c90b22f-9450-40f7-8abb-82c5e11ff1292022-03-26T12:37:56ZTNF and TNFR polymorphisms in severe sepsis and septic shock: a prospective multicentre study.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2c90b22f-9450-40f7-8abb-82c5e11ff129EnglishSymplectic Elements at Oxford2004Gordon, ALagan, AAganna, ECheung, LPeters, CMcDermott, MMillo, JWelsh, KHolloway, PHitman, GPiper, RGarrard, CHinds, CTumour necrosis factor (TNF) is an important pro-inflammatory cytokine produced in sepsis. Studies examining the association of individual TNF single nucleotide polymorphisms with sepsis have produced conflicting results. This study investigated whether common polymorphisms of the TNF locus and the two receptor genes, TNFRSF1A and TNFRSF1B, influence circulating levels of encoded proteins, and whether individual polymorphisms or extended haplotypes of these genes are associated with susceptibility, severity of illness or outcome in adult patients with severe sepsis or septic shock. A total of 213 Caucasian patients were recruited from eight intensive care units (ICU) in the UK and Australia. Plasma levels of TNF (P = 0.02), sTNFRSF1A (P = 0.005) and sTNFRSF1B (P = 0.01) were significantly higher in those who died on ICU compared to those who survived. There was a positive correlation between increasing soluble receptor levels and organ dysfunction (increasing SOFA score) (sTNFRSF1A R = 0.51, P < 0.001; sTNFRSF1B R = 0.53, P < 0.001), and in particular with the degree of renal dysfunction. In this study, there were no significant associations between the selected candidate TNF or TNF receptor polymorphisms, or their haplotypes, and susceptibility to sepsis, illness severity or outcome. The influence of polymorphisms of the TNF locus on susceptibility to, and outcome from sepsis remains uncertain.
spellingShingle Gordon, A
Lagan, A
Aganna, E
Cheung, L
Peters, C
McDermott, M
Millo, J
Welsh, K
Holloway, P
Hitman, G
Piper, R
Garrard, C
Hinds, C
TNF and TNFR polymorphisms in severe sepsis and septic shock: a prospective multicentre study.
title TNF and TNFR polymorphisms in severe sepsis and septic shock: a prospective multicentre study.
title_full TNF and TNFR polymorphisms in severe sepsis and septic shock: a prospective multicentre study.
title_fullStr TNF and TNFR polymorphisms in severe sepsis and septic shock: a prospective multicentre study.
title_full_unstemmed TNF and TNFR polymorphisms in severe sepsis and septic shock: a prospective multicentre study.
title_short TNF and TNFR polymorphisms in severe sepsis and septic shock: a prospective multicentre study.
title_sort tnf and tnfr polymorphisms in severe sepsis and septic shock a prospective multicentre study
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