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


METHODS
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.
Barber
R C
RC
The Department of Surgery, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9160, USA. robert.barber@utsouthwestern.edu
Aragaki
C C
CC
Rivera-Chavez
F A
FA
Purdue
G F
GF
Hunt
J L
JL
Horton
J W
JW
D000328:Adult; D002056:Burns / Q000150:complications*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000235:genetics*; D012307:Risk Factors; D018805:Sepsis / Q000175:diagnosis / Q000235:genetics*; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha