title: Toll-like receptor 1 polymorphisms and associated outcomes in sepsis after traumatic injury: a candidate gene association study.
abstract: OBJECTIVE
  To determine whether single nucleotide polymorphisms (SNPs) in TLR1 are associated with mortality, specifically sepsis-associated mortality, in a traumatically injured population.
  
  
  BACKGROUND
  Innate immune responses mediated by toll-like receptors (TLRs) induce early inflammatory responses to pathogen and damage-associated molecular patterns. Genetic variation in TLRs has been associated with susceptibility and outcomes in a number of infectious and noninfectious disease states.
  
  
  METHODS
  Patients admitted to the trauma intensive care unit at a level 1 trauma center serving 4 states were enrolled and followed for development of infection, sepsis, and death. Genomic DNA was genotyped and logistic regression analysis was performed to determine associations between TLR1 SNPs and mortality. We further examined for associations between TLR1 SNPs and mortality in subgroups on the basis of the presence of sepsis and the type of sepsis-associated organism.
  
  
  RESULTS
  We enrolled 1961 patients. TLR1-7202G (rs5743551) was associated with increased mortality after traumatic injury and this association was primarily observed in the subset of patients who developed sepsis [adjusted odds ratio (OR): 3.16; 95% confidence interval (CI): 1.43-6.97, P=0.004]. This association persisted after further restriction to gram-positive sepsis. TLR1(742A/G(Asn248Ser)) (rs4833095), a coding SNP in LD with TLR1-7202G, was also associated with mortality in gram-positive sepsis (adjusted OR: 4.16; 95% CI: 1.22-14.19, P=0.023).
  
  
  CONCLUSIONS
  Genetic variation in TLR1 is associated with increased mortality in patients with sepsis after traumatic injury and may represent a novel marker of risk for death in critically injured patients.
authors.affiliation: *Department of Surgery †Division of Pulmonary and Critical Care Medicine, University of Washington, Harborview Medical Center, Seattle, WA.
authors.forename: Callie M
authors.initials: CM
authors.lastname: Thompson
authors.forename: Tarah D
authors.initials: TD
authors.lastname: Holden
authors.forename: Gail
authors.initials: G
authors.lastname: Rona
authors.forename: Balaji
authors.initials: B
authors.lastname: Laxmanan
authors.forename: R Anthony
authors.initials: RA
authors.lastname: Black
authors.forename: Grant E
authors.initials: GE
authors.lastname: OʼKeefe
authors.forename: Mark M
authors.initials: MM
authors.lastname: Wurfel
mesh_terms: D000328:Adult; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007113:Immunity, Innate; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018805:Sepsis / Q000209:etiology / Q000235:genetics* / Q000401:mortality*; D051194:Toll-Like Receptor 1 / Q000235:genetics*; D014947:Wounds and Injuries / Q000150:complications*; D055815:Young Adult
chemical_list: D051194:Toll-Like Receptor 1