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TLR4 and TNF-α polymorphisms are associated with an increased risk for severe sepsis following burn injury
  1. R C Barber1,
  2. C C Aragaki2,
  3. F A Rivera-Chavez1,
  4. G F Purdue1,
  5. J L Hunt1,
  6. J W Horton1
  1. 1The Department of Surgery, The University of Texas Southwestern Medical Center, Dallas, TX, USA
  2. 2Divisions of Epidemiology and Biostatistics, School of Public Health, Dallas Regional Campus, University of Texas Health Science Center at Houston, Dallas, TX, USA
  1. Correspondence to:
 Dr Robert C Barber
 UT Southwestern Medical Center, Department of Surgery, 5323 Harry Hines Blvd, Dallas, TX 75390-9160, USA;


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 −308, 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.

  • aOR, adjusted odds ratio
  • BICU, burn intensive care unit
  • ISS, injury severity score
  • LPS, lipopolysaccharide
  • PCR, polymerase chain reaction
  • SNPs, single nucleotide polymorphisms
  • TBSA, total body surface area
  • burns
  • polymorphism
  • sepsis
  • TLR4
  • TNF-α

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  • This work was supported by NIGMS grant #5P50GM021681-38.

  • Conflict of interest: none declared.