title: Polymorphisms in the toll-like receptor 9 gene associated with sepsis and multiple organ dysfunction after major blunt trauma.
abstract: BACKGROUND
  Toll-like receptor (TLR) 9 is the pattern recognition receptor for microbial DNA. Genetic variation within pattern recognition receptors for bacterial endotoxin and exotoxin has been shown to be associated with the risk of sepsis and organ dysfunction in critical illness. However, little is known about the clinical relevance of TLR9 gene polymorphisms in critical illness.
  
  
  METHODS
  A total of 557 patients with major blunt trauma were included in the study. Genetic variation data for the entire TLR9 gene were obtained from the HapMap Project. The genotypes of TLR9 gene polymorphisms were determined using a pyrosequencing method. Whole peripheral blood samples obtained immediately after admission were stimulated with bacterial DNA and production of tumour necrosis factor (TNF) α was then determined. Sepsis morbidity rate and multiple organ dysfunction (MOD) scores were assessed.
  
  
  RESULTS
  Of five single-nucleotide polymorphisms (SNPs) genotyped, four (rs187084, rs352139, rs352140 and rs352162) existed as common SNPs and were in strong linkage disequilibrium. Both rs187084 and rs352162 were significantly associated with TNF-α production by peripheral blood leucocytes in response to bacterial DNA stimulation and a higher sepsis morbidity rate in patients with major trauma. In addition, the rs352162 polymorphism was significantly associated with MOD scores, whereas rs187084 showed a trend to be associated with MOD score.
  
  
  CONCLUSIONS
  TLR9 polymorphisms rs187084 and rs352162 might be used to provide relevant risk estimates for the development of sepsis and MOD in patients with major trauma.
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Chongqing, China.
authors.forename: K-H
authors.initials: KH
authors.lastname: Chen
authors.forename: L
authors.initials: L
authors.lastname: Zeng
authors.forename: W
authors.initials: W
authors.lastname: Gu
authors.forename: J
authors.initials: J
authors.lastname: Zhou
authors.forename: D-Y
authors.initials: DY
authors.lastname: Du
authors.forename: J-X
authors.initials: JX
authors.lastname: Jiang
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018805:Sepsis / Q000235:genetics*; D051217:Toll-Like Receptor 9 / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014949:Wounds, Nonpenetrating / Q000235:genetics*; D055815:Young Adult
chemical_list: D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha