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J Med Genet. 2004 November; 41(11): 808–813.
PMCID: PMC1383768

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


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 [gt-or-equal, slanted]20% of their total body surface area or any smoke inhalation injury without significant non-burn related trauma (injury severity score (ISS)[gt-or-equal, slanted]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-1ß –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.

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Selected References

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