Polymorphism in the tissue factor region is associated with basal but not endotoxin-induced tissue factor-mRNA levels in leukocytes.
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.
Marsik
C
C
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
Endler
G
G
Halama
T
T
Schlifke
I
I
Mustafa
S
S
Hysjulien
J L
JL
Key
N S
NS
Jilma
B
B
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
D004731:Endotoxins; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013925:Thromboplastin