title: The presence of functionally relevant toll-like receptor polymorphisms does not significantly correlate with development or outcome of sepsis.
abstract: OBJECTIVE
  Members of the toll-like receptor (TLR) family have been shown to play important roles in inflammatory responses. Single-nucleotide polymorphisms (SNPs) altering receptor activity may either have detectable effects or might be without results due to compensatory mechanisms. We determined the genotype frequencies of functionally relevant SNPs in TLR2, 4 and 5 in critically ill patients (n=150) from a multidisciplinary surgical intensive care unit (ICU). The inflammatory response (procalcitonin, C-reactive protein, white blood count) and clinical classification (Acute Physiology and Chronic Health Evaluation Score II, Simplified Acute Physiology Score II, Sepsis-related Organ Failure Assessment) were monitored daily.
  
  
  RESULTS
  The genetic polymorphisms correlate with neither development nor outcome of sepsis. No correlations were found between C-reactive protein or WBC and the investigated SNPs. In patients in the ICU with abdominal surgery and multiple trauma, the TLR2-R753Q SNP was associated with infection at ICU admission (p<0.01); and for carriers of the TLR4-D299G SNP, a trend was observed (p=0.0776). Patients with multiple trauma carrying the TLR4-D299G SNP displayed significantly higher levels of procalcitonin (p=0.0212).
  
  
  CONCLUSIONS
  None of the investigated SNPs clearly predicted outcome of sepsis-related multiorgan failure. TLR2-R753Q SNP may be a useful marker to identify patients with high risk to develop infections at ICU admission but should be validated in larger studies. Future SNP-arrays investigating predisposition for infection should include this SNP alone or in combination with other functionally relevant SNPs.
authors: Institute for Clinical Chemistry, University Hospital Mannheim, Mannheim, Germany.
authors: Parviz
authors: P
authors: Ahmad-Nejad
authors: Christof
authors: C
authors: Denz
authors: Wilma
authors: W
authors: Zimmer
authors: Jennifer
authors: J
authors: Wacker
authors: Peter
authors: P
authors: Bugert
authors: Christel
authors: C
authors: Weiss
authors: Michael
authors: M
authors: Quintel
authors: Michael
authors: M
authors: Neumaier
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003422:Critical Care / Q000706:statistics & numerical data; D018450:Disease Progression; D004636:Emergency Service, Hospital / Q000706:statistics & numerical data; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D011379:Prognosis; D012189:Retrospective Studies; D018805:Sepsis / Q000150:complications / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D051198:Toll-Like Receptor 5 / Q000235:genetics*; D055815:Young Adult
chemical_list: C495342:TLR2 protein, human; C495345:TLR4 protein, human; C495346:TLR5 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5