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Blood, 15 March 2005, Vol. 105, No. 6, pp. 2380-2383. Prepublished online as a Blood First Edition Paper on November 16, 2004; DOI 10.1182/blood-2004-09-3752.
Submitted September 28, 2004
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria * Corresponding author; email: bernd.jilma{at}meduniwien.ac.at.
The single nucleotide polymorphism (SNP) Ser128Arg in the E-selectin gene is over-represented in certain patient groups with atherosclerosis or restenosis. We hypothesized and tested whether it may affect cytokine induced levels of soluble (s)E-selectin, or be associated with pro-inflammatory or pro-coagulant properties in a well standardized inflammation model.
Healthy male volunteers (n=157) received an LPS-infusion, were genotyped for the S128R SNP and outcome parameters were measured by enzyme immunoassays and real time polymerase chain reaction (RT-PCR, Taqman). The S128R SNP had no pronounced effects on basal or inducible sE-selectin levels, or levels of tumor necrosis factor or interleukin-6. However, carriers of the S128R SNP had 20% higher monocyte counts at 24h. Importantly, the S128R allele enhanced thrombin generation by 50-80% as measured by prothrombin fragment F1+2 (p< 0.01), and hence fibrin formation (D-dimer) 2-fold (p=0.01 to p=0.002). However, tissue factor (TF)-mRNA levels were not affected.
The S128R E-selectin genotype is associated with pro-coagulant effects in a human model of endotoxin induced, TF-triggered coagulation. This could contribute to its linkage with various thrombotic cardiovascular disorders.
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