title: Polymorphism in the tissue factor region is associated with basal but not endotoxin-induced tissue factor-mRNA levels in leukocytes.
abstract: OBJECTIVE
  Tissue factor (TF) plays a central role during disseminated intravascular coagulation (DIC) in sepsis. We hypothesized that a frequent D/I polymorphism, at nucleotide position -1208 in the promoter region, could influence TF-mRNA and downstream coagulation.
  
  
  METHODS
  Basal- and lipopolysaccharide (LPS)-induced TF-mRNA expression, microparticle-associated TF-procoagulant activity and coagulation were determined in healthy men (n = 74) before and after endotoxin (LPS) infusion (2 ng kg(-1)). Basal values of TF-mRNA ranged between 34 and > 37.5 cycles.
  
  
  RESULTS
  Baseline TF-mRNA levels significantly differed between genotypes: I/I carriers had almost 2-fold higher TF-mRNA levels compared to D/D carriers at baseline (P < 0.01). In accordance, higher levels of microparticle-associated TF-procoagulant activity could be seen in I/I carriers. However, the genotype did not affect basal or LPS-induced levels of prothrombin fragment F1+2, D-dimer or cytokines including tumor necrosis factor and interleukin-6.
  
  
  CONCLUSIONS
  The TF-1208 polymorphism is functional in that it regulates basal TF-mRNA in circulating monocytes and circulating microparticle-associated TF-procoagulant activity in vivo, but does not influence the relative increase in TF-mRNA or coagulation activation during low-grade endotoxemia.
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Marsik
authors.forename: G
authors.initials: G
authors.lastname: Endler
authors.forename: T
authors.initials: T
authors.lastname: Halama
authors.forename: I
authors.initials: I
authors.lastname: Schlifke
authors.forename: S
authors.initials: S
authors.lastname: Mustafa
authors.forename: J L
authors.initials: JL
authors.lastname: Hysjulien
authors.forename: N S
authors.initials: NS
authors.lastname: Key
authors.forename: B
authors.initials: B
authors.lastname: Jilma
mesh_terms: D004211:Disseminated Intravascular Coagulation / Q000235:genetics; D019446:Endotoxemia / Q000235:genetics; D004731:Endotoxins / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology* / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000378:metabolism; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D013925:Thromboplastin / Q000235:genetics* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D004731:Endotoxins; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013925:Thromboplastin