title: Polymorphisms of the toll-like receptor 2 and 4 genes are associated with faster progression and a more severe course of sepsis in critically ill patients.
abstract: OBJECTIVE
  To determine whether the Arg753Gln polymorphism of the toll-like receptor 2 (TLR2) gene and the Asp299Gly polymorphism of the TLR4 gene in critically ill patients affect their clinical outcomes.
  
  
  METHODS
  Medical and surgical patients in three intensive care units (ICU) were enrolled in this prospective study. TLR2 and TLR4 gene polymorphisms were determined using restriction fragment length polymorphism analysis.
  
  
  RESULTS
  A total of 145 patients were included in this study: 28 patients carried heterozygous mutations (10 in the TLR2 gene, 19 in the TLR4 gene, and one combined) and 117 patients were wild type. Severe sepsis was observed in 33% of wild types (n = 38), 60% of the TLR2 group (n = 6), and 63% of the TLR4 group (n = 12); the difference was significant between the TLR4 and wild type groups. Both TLR groups demonstrated a shorter time-to-onset of severe sepsis or septic shock. Only the TLR4 group demonstrated significant progression towards septic shock compared with the wild type group. Length of ICU stay was significantly prolonged in the TLR4 group compared with the wild type group, but not in the TLR2 group.
  
  
  CONCLUSIONS
  Two common SNPs of the TLR2 and TLR4 genes--Arg753Gln and Asp299Gly--were associated with a shorter time-to-onset of severe sepsis or septic shock in patients admitted to the ICU.
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, Charité - Universitätsmedizin Berlin, Campus Charité Mitte and Campus Virchow-Klinikum, Berlin, Germany.
authors.forename: Irit
authors.initials: I
authors.lastname: Nachtigall
authors.forename: Andrey
authors.initials: A
authors.lastname: Tamarkin
authors.forename: Sascha
authors.initials: S
authors.lastname: Tafelski
authors.forename: Andreas
authors.initials: A
authors.lastname: Weimann
authors.forename: Andreas
authors.initials: A
authors.lastname: Rothbart
authors.forename: Susanne
authors.initials: S
authors.lastname: Heim
authors.forename: Klaus D
authors.initials: KD
authors.lastname: Wernecke
authors.forename: Claudia
authors.initials: C
authors.lastname: Spies
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D016638:Critical Illness; D017931:DNA Primers; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D007362:Intensive Care Units; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000235:genetics / Q000503:physiopathology*; D012720:Severity of Illness Index; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D051197:Toll-Like Receptor 4 / Q000235:genetics*
chemical_list: D017931:DNA Primers; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4
keywords: Arg753Gln polymorphism; Asp299Gly polymorphism; Toll-like receptor 2; septic shock; toll-like receptor 4