| |
|
|
|
|
|
|
|||
|
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.
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY The single nucleotide polymorphism Ser128Arg in the E-selectin gene is associated with enhanced coagulation during human endotoxemiaFrom 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.
This article has been cited by other articles:
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||
| Copyright © 2005 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||||