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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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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY

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

From the Department of Clinical Pharmacology, the Clinical Institute for Medical and Chemical Laboratory Diagnostics, and the Department of Blood Group Serology and Transfusion Medicine, Medical University Vienna, Austria.

The single nucleotide polymorphism (SNP) Ser128Arg in the E-selectin gene is overrepresented 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 proinflammatory or procoagulant properties in a well-standardized inflammation model. Healthy male volunteers (n = 157) received a lipopolysaccharide (LPS) infusion and 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 24 hours after LPS infusion. Importantly, the S128R allele enhanced thrombin generation by 50% to 80%, as measured by prothrombin fragment F1+2 (P < .01), and hence fibrin formation (D-dimer) 2-fold (P = .01 to P = .002). However, tissue factor (TF) mRNA levels were not affected. The S128R E-selectin genotype is associated with procoagulant 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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