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J Med Genet. 2004 Nov;41(11):808-13.

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

Author information

  • 1The Department of Surgery, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9160, USA. robert.barber@utsouthwestern.edu

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 > or =20% of their total body surface area or any smoke inhalation injury without significant non-burn related trauma (injury severity score (ISS)> or =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-alpha -308, IL-1beta -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-alpha -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-alpha -308 polymorphisms were significantly associated with an increased risk for severe sepsis following burn trauma.

PMID:
15520404
PMCID:
PMC1383768
DOI:
10.1136/jmg.2004.021600
[PubMed - indexed for MEDLINE]
Free PMC Article
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