CD14-159 C allele is associated with increased risk of mortality after burn injury

Robert C. Barber, Corinne C. Aragaki, Ling Yu E Chang, Gary F. Purdue, John L. Hunt, Brett D. Arnoldo, Jureta W. Horton

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Although comprehension of postburn pathophysiology has grown in recent years, we are still unable to accurately identify burn patients who are at an increased risk of infectious complications and death. This unexplained variation is likely influenced by heritable factors; the genetic predisposition for death from infection has been estimated as greater than that for cardiovascular disease or cancer. Identify genetic variants associated with increased mortality after burn injury. A total of 233 patients with burns of 15% of total body surface area or greater or smoke inhalation injury who survived more than 48 h after admission and were without significant nonburn-related trauma (injury severity score ≥16), traumatic or anoxic brain injury, or spinal cord injury. We examined the influence of genotype at five candidate loci (interleukin [IL]-1β, IL-6, tumor necrosis factor-α, toll-like receptor 4, CD14) on mortality risk after burn injury. DNA was isolated from residual blood from laboratory draws and candidate genotypes were determined by real-time polymerase chain reaction using TaqMan probes. Clinical data were prospectively collected into a local, curated database. Allelic associations were analyzed by multivariate logistic regression. After adjustment for age, full-thickness burn size, inhalation injury, ethnicity, and sex, carriage of the CD14-159 C allele imparted at least a 1.3-fold increased risk for death after burn injury, relative to TT homozygotes (adjusted odds ratio, 2.9; 95% confidence interval, 1.3 - 6.8; P = 0.01). This association was stronger (adjusted odds ratio, 3.3; 95% confidence interval, 1.3 - 8.4; P = 0.01) when the analysis was conducted only on deaths accompanied by severe sepsis. In addition, a gene dosage effect for increased mortality was apparent for carriage of the CD14-159 C allele (P = 0.006). The gene dosage effect remained when white, Hispanic, or African American patients were analyzed independently, although statistical significance was not achieved in the subgroup analysis. None of the other single nucleotide polymorphisms examined were significantly associated with mortality. These data provide strong evidence that a CD14 promoter allele that is known to impart lower baseline and induced CD14 transcription also affects mortality risk after burn injury. A potential (although untested) mechanism for our observation is that reduced signaling through CD14/toll-like receptor 4 in response to challenge by gram-negative bacteria after burns results in a blunted innate immune response and subsequent increased likelihood for systemic infection and death.

Original languageEnglish (US)
Pages (from-to)232-237
Number of pages6
JournalShock
Volume27
Issue number3
DOIs
StatePublished - Mar 2007

Fingerprint

Alleles
Mortality
Wounds and Injuries
Toll-Like Receptor 4
Gene Dosage
Burns
Inhalation Burns
Smoke Inhalation Injury
Odds Ratio
Genotype
Confidence Intervals
Injury Severity Score
Body Surface Area
Homozygote
Genetic Predisposition to Disease
Infection
Gram-Negative Bacteria
Spinal Cord Injuries
Interleukin-1
Hispanic Americans

Keywords

  • Burn injury
  • CD14
  • Innate immunity
  • Mortality
  • Polymorphism
  • SNP

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Physiology

Cite this

Barber, R. C., Aragaki, C. C., Chang, L. Y. E., Purdue, G. F., Hunt, J. L., Arnoldo, B. D., & Horton, J. W. (2007). CD14-159 C allele is associated with increased risk of mortality after burn injury. Shock, 27(3), 232-237. https://doi.org/10.1097/01.shk.0000239770.10528.9a

CD14-159 C allele is associated with increased risk of mortality after burn injury. / Barber, Robert C.; Aragaki, Corinne C.; Chang, Ling Yu E; Purdue, Gary F.; Hunt, John L.; Arnoldo, Brett D.; Horton, Jureta W.

In: Shock, Vol. 27, No. 3, 03.2007, p. 232-237.

Research output: Contribution to journalArticle

Barber, RC, Aragaki, CC, Chang, LYE, Purdue, GF, Hunt, JL, Arnoldo, BD & Horton, JW 2007, 'CD14-159 C allele is associated with increased risk of mortality after burn injury', Shock, vol. 27, no. 3, pp. 232-237. https://doi.org/10.1097/01.shk.0000239770.10528.9a
Barber, Robert C. ; Aragaki, Corinne C. ; Chang, Ling Yu E ; Purdue, Gary F. ; Hunt, John L. ; Arnoldo, Brett D. ; Horton, Jureta W. / CD14-159 C allele is associated with increased risk of mortality after burn injury. In: Shock. 2007 ; Vol. 27, No. 3. pp. 232-237.
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