Factor XIII Val34Leu polymorphism and recurrent myocardial infarction in patients with coronary artery disease |
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Authors: | Rolf P Kreutz Abbas Bitar Janelle Owens Zeruesenay Desta Jeffrey A Breall Elisabeth von der Lohe Anjan Sinha Matteo Vatta Perry Nystrom Yan Jin David A Flockhart |
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Institution: | 1. Krannert Institute of Cardiology, Indiana University School of Medicine, 1800?N. Capitol Ave, ME-400, Indianapolis, IN, 46202, USA 2. Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN, USA 3. Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA
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Abstract: | Factor XIII (FXIII) is necessary for cross linking of fibrin strands and generation of stable fibrin clot. FXIII Val34Leu is a common genetic single nucleotide polymorphism that has been associated with accelerated fibrin stabilization and reduced rate of fibrinolysis. The contribution of Val34Leu to long term risk of recurrent myocardial infarction (MI) in patients with coronary stenting has not been conclusively established. The objective of the study was to examine the effects of Val34Leu on fibrin generation, platelet aggregation, and long term clinical outcomes in patients with coronary artery disease treated with dual antiplatelet therapy. Patients with angiographically documented coronary artery disease who were treated with aspirin and clopidogrel were enrolled (n = 211). Light transmittance aggregometry and plasma fibrin clot formation using thrombelastography (TEG) were determined. Genotyping of Val34Leu was performed using Taqman assay. Clinical events during follow up were recorded. Homozygous carriers of 34Leu variant had significantly shorter fibrin clot formation time as compared to wild type individuals (TEG K: 1.27 ± 0.3 vs. 1.68 ± 1.1 min, p = 0.011). The Val34Leu variant was associated with gene dose dependent increased risk of MI (log rank, p = 0.002) or occurrence of composite of MI and CV death (log rank, p = 0.005) with highest event rates observed in homozygous carriers of 34Leu. In summary, FXIII Val34Leu polymorphism was associated with increased rate of fibrin stabilization in homozygous carriers of the variant and may increase risk of recurrent MI and death in patients with angiographically established coronary artery disease treated with dual antiplatelet therapy. |
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