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

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126 Scopus citations

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 1 2004

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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