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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.


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Submitted September 28, 2004
Accepted November 8, 2004

The single nucleotide polymorphism Ser128Arg in the E-selectin gene is associated with enhanced coagulation during human endotoxemia

Bernd Jilma*, Claudia Marsik, Florian Kovar, Oswald F Wagner, Petra Jilma-Stohlawetz, and Georg Endler

Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria; Clinical Institute for Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna, Austria
Clinical Institute for Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna, Austria
Department of Blood Group Serology and Transfusion Medicine, 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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Arch Intern MedHome page
B. Jilma, F. M. Kovar, G. Hron, G. Endler, C. L. Marsik, S. Eichinger, and P. A. Kyrle
Homozygosity in the Single Nucleotide Polymorphism Ser128Arg in the E-Selectin Gene Associated With Recurrent Venous Thromboembolism.
Arch Intern Med, August 14, 2006; 166(15): 1655 - 1659.
[Abstract] [Full Text] [PDF]



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