TLR4 and TNF-α polymorphisms are associated with an increased risk for severe sepsis following burn injury

Robert C. Barber, C. C. Aragaki, F. A. Rivera-Chavez, G. F. Purdue, J. L. Hunt, J. W. Horton

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

Context: Sepsis, organ failure, and shock remain common among patients with moderate to severe burn injuries. The inability of clinical factors to identify at-risk patients suggests that genetic variation may influence the risk for serious infection and the outcome from severe injury. Objective: Resolution of genetic variants associated with severe sepsis following burn injury. Patients: A total of 159 patients with burns ≥20% of their total body surface area or any smoke inhalation injury without significant non-burn related trauma (injury severity score (ISS)≥16), traumatic or anoxic brain injury, or spinal cord injury and who survived more than 48 h post-admission. Methods: Candidate single nucleotide polymorphisms (SNPs) within bacterial recognition (TLR4 +896, CD14-159) and inflammatory response (TNF-α -3O8, IL-1β -31, IL-6 -174) loci were evaluated for association with increased risk for severe sepsis (sepsis plus organ dysfunction or septic shock) and mortality. Results: After adjustment for age, full-thickness burn size, ethnicity, and gender, carriage of the TLR4 +896 G-allele imparted at least a 1.8-fold increased risk of developing severe sepsis following a burn injury, relative to AA homozygotes (adjusted odds ratio (aOR) 6.4; 95% confidence interval (CI) 1.8 to 23.2). Carriage of the TNF-α -308 A-allele imparted a similarly increased risk, relative to GG homozygotes (aOR = 4.5; 95% CI 1.7 to 12.0). None of the SNPs examined were significantly associated with mortality. Conclusions: The TLR4 +896 and TNF-α -308 polymorphisms were significantly associated with an increased risk for severe sepsis following burn trauma.

Original languageEnglish (US)
Pages (from-to)808-813
Number of pages6
JournalJournal of Medical Genetics
Volume41
Issue number11
DOIs
StatePublished - Nov 2004

Fingerprint

Sepsis
Wounds and Injuries
Homozygote
Single Nucleotide Polymorphism
Smoke Inhalation Injury
Alleles
Odds Ratio
Confidence Intervals
Injury Severity Score
Mortality
Body Surface Area
Septic Shock
Spinal Cord Injuries
Interleukin-1
Burns
Brain Injuries
Shock
Interleukin-6
Infection

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Barber, R. C., Aragaki, C. C., Rivera-Chavez, F. A., Purdue, G. F., Hunt, J. L., & Horton, J. W. (2004). TLR4 and TNF-α polymorphisms are associated with an increased risk for severe sepsis following burn injury. Journal of Medical Genetics, 41(11), 808-813. https://doi.org/10.1136/jmg.2004.021600

TLR4 and TNF-α polymorphisms are associated with an increased risk for severe sepsis following burn injury. / Barber, Robert C.; Aragaki, C. C.; Rivera-Chavez, F. A.; Purdue, G. F.; Hunt, J. L.; Horton, J. W.

In: Journal of Medical Genetics, Vol. 41, No. 11, 11.2004, p. 808-813.

Research output: Contribution to journalArticle

Barber, RC, Aragaki, CC, Rivera-Chavez, FA, Purdue, GF, Hunt, JL & Horton, JW 2004, 'TLR4 and TNF-α polymorphisms are associated with an increased risk for severe sepsis following burn injury', Journal of Medical Genetics, vol. 41, no. 11, pp. 808-813. https://doi.org/10.1136/jmg.2004.021600
Barber, Robert C. ; Aragaki, C. C. ; Rivera-Chavez, F. A. ; Purdue, G. F. ; Hunt, J. L. ; Horton, J. W. / TLR4 and TNF-α polymorphisms are associated with an increased risk for severe sepsis following burn injury. In: Journal of Medical Genetics. 2004 ; Vol. 41, No. 11. pp. 808-813.
@article{21658132af5b426299a82d0edf00fbf0,
title = "TLR4 and TNF-α polymorphisms are associated with an increased risk for severe sepsis following burn injury",
abstract = "Context: Sepsis, organ failure, and shock remain common among patients with moderate to severe burn injuries. The inability of clinical factors to identify at-risk patients suggests that genetic variation may influence the risk for serious infection and the outcome from severe injury. Objective: Resolution of genetic variants associated with severe sepsis following burn injury. Patients: A total of 159 patients with burns ≥20{\%} of their total body surface area or any smoke inhalation injury without significant non-burn related trauma (injury severity score (ISS)≥16), traumatic or anoxic brain injury, or spinal cord injury and who survived more than 48 h post-admission. Methods: Candidate single nucleotide polymorphisms (SNPs) within bacterial recognition (TLR4 +896, CD14-159) and inflammatory response (TNF-α -3O8, IL-1β -31, IL-6 -174) loci were evaluated for association with increased risk for severe sepsis (sepsis plus organ dysfunction or septic shock) and mortality. Results: After adjustment for age, full-thickness burn size, ethnicity, and gender, carriage of the TLR4 +896 G-allele imparted at least a 1.8-fold increased risk of developing severe sepsis following a burn injury, relative to AA homozygotes (adjusted odds ratio (aOR) 6.4; 95{\%} confidence interval (CI) 1.8 to 23.2). Carriage of the TNF-α -308 A-allele imparted a similarly increased risk, relative to GG homozygotes (aOR = 4.5; 95{\%} CI 1.7 to 12.0). None of the SNPs examined were significantly associated with mortality. Conclusions: The TLR4 +896 and TNF-α -308 polymorphisms were significantly associated with an increased risk for severe sepsis following burn trauma.",
author = "Barber, {Robert C.} and Aragaki, {C. C.} and Rivera-Chavez, {F. A.} and Purdue, {G. F.} and Hunt, {J. L.} and Horton, {J. W.}",
year = "2004",
month = "11",
doi = "10.1136/jmg.2004.021600",
language = "English (US)",
volume = "41",
pages = "808--813",
journal = "Journal of Medical Genetics",
issn = "0022-2593",
publisher = "BMJ Publishing Group",
number = "11",

}

TY - JOUR

T1 - TLR4 and TNF-α polymorphisms are associated with an increased risk for severe sepsis following burn injury

AU - Barber, Robert C.

AU - Aragaki, C. C.

AU - Rivera-Chavez, F. A.

AU - Purdue, G. F.

AU - Hunt, J. L.

AU - Horton, J. W.

PY - 2004/11

Y1 - 2004/11

N2 - Context: Sepsis, organ failure, and shock remain common among patients with moderate to severe burn injuries. The inability of clinical factors to identify at-risk patients suggests that genetic variation may influence the risk for serious infection and the outcome from severe injury. Objective: Resolution of genetic variants associated with severe sepsis following burn injury. Patients: A total of 159 patients with burns ≥20% of their total body surface area or any smoke inhalation injury without significant non-burn related trauma (injury severity score (ISS)≥16), traumatic or anoxic brain injury, or spinal cord injury and who survived more than 48 h post-admission. Methods: Candidate single nucleotide polymorphisms (SNPs) within bacterial recognition (TLR4 +896, CD14-159) and inflammatory response (TNF-α -3O8, IL-1β -31, IL-6 -174) loci were evaluated for association with increased risk for severe sepsis (sepsis plus organ dysfunction or septic shock) and mortality. Results: After adjustment for age, full-thickness burn size, ethnicity, and gender, carriage of the TLR4 +896 G-allele imparted at least a 1.8-fold increased risk of developing severe sepsis following a burn injury, relative to AA homozygotes (adjusted odds ratio (aOR) 6.4; 95% confidence interval (CI) 1.8 to 23.2). Carriage of the TNF-α -308 A-allele imparted a similarly increased risk, relative to GG homozygotes (aOR = 4.5; 95% CI 1.7 to 12.0). None of the SNPs examined were significantly associated with mortality. Conclusions: The TLR4 +896 and TNF-α -308 polymorphisms were significantly associated with an increased risk for severe sepsis following burn trauma.

AB - Context: Sepsis, organ failure, and shock remain common among patients with moderate to severe burn injuries. The inability of clinical factors to identify at-risk patients suggests that genetic variation may influence the risk for serious infection and the outcome from severe injury. Objective: Resolution of genetic variants associated with severe sepsis following burn injury. Patients: A total of 159 patients with burns ≥20% of their total body surface area or any smoke inhalation injury without significant non-burn related trauma (injury severity score (ISS)≥16), traumatic or anoxic brain injury, or spinal cord injury and who survived more than 48 h post-admission. Methods: Candidate single nucleotide polymorphisms (SNPs) within bacterial recognition (TLR4 +896, CD14-159) and inflammatory response (TNF-α -3O8, IL-1β -31, IL-6 -174) loci were evaluated for association with increased risk for severe sepsis (sepsis plus organ dysfunction or septic shock) and mortality. Results: After adjustment for age, full-thickness burn size, ethnicity, and gender, carriage of the TLR4 +896 G-allele imparted at least a 1.8-fold increased risk of developing severe sepsis following a burn injury, relative to AA homozygotes (adjusted odds ratio (aOR) 6.4; 95% confidence interval (CI) 1.8 to 23.2). Carriage of the TNF-α -308 A-allele imparted a similarly increased risk, relative to GG homozygotes (aOR = 4.5; 95% CI 1.7 to 12.0). None of the SNPs examined were significantly associated with mortality. Conclusions: The TLR4 +896 and TNF-α -308 polymorphisms were significantly associated with an increased risk for severe sepsis following burn trauma.

UR - http://www.scopus.com/inward/record.url?scp=8744301714&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=8744301714&partnerID=8YFLogxK

U2 - 10.1136/jmg.2004.021600

DO - 10.1136/jmg.2004.021600

M3 - Article

C2 - 15520404

AN - SCOPUS:8744301714

VL - 41

SP - 808

EP - 813

JO - Journal of Medical Genetics

JF - Journal of Medical Genetics

SN - 0022-2593

IS - 11

ER -