IN FOCUS: Polymorphism in the tissue factor region is associated with basal but not endotoxin-induced tissue factor-mRNA levels in leukocytes

• Published in: Journal of thrombosis and haemostasis Vol. 4; no. 4; pp. 745 - 749
• Main Authors: Marsik, C, Endler, G, Halama, T, Schlifke, I, Mustafa, S, Hysjulien, J L, Key, N S, Jilma, B
• Format: Journal Article
• Language: English
• Published: 01-04-2006
• ISSN: 1538-7933; 1538-7836
• DOI: 10.1111/j.1538-7836.2006.01854.x

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 super(-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 F sub(1+2), D-dimer or cytokines including tumor necrosis factor and interleukin-6. Conclusion: 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.