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Stroke Research and Treatment
Volume 2011 (2011), Article ID 424759, 6 pages
Research Article

Factor VII Activating Protease Polymorphism (G534E) Is Associated with Increased Risk for Stroke and Mortality

1Department of Cardiology, Leiden University Medical Center, C5-P, P.O. Box 9600, 2300 RC Leiden, The Netherlands
2Department of Gerontology and Geriatrics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
3Interuniversity Cardiology Institute of the Netherlands (ICIN), 3501 DG Utrecht, The Netherlands
4Einthoven Laboratory for Experimental Vascular Medicine, 2333 ZA Leiden, The Netherlands
5Department of Biochemistry, Justus-Liebig-University, 35392 Giessen, Germany
6Department of Epidemiology & Department of Radiology, Erasmus MC University Medical Center, 3000 CA Rotterdam, The Netherlands
7Department of Medical Statistics, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands
8Department of Cardiology, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands
9Department of Cardiology, University Medical Center Groningen, 9700 RB Groningen, The Netherlands
10Department of Cardiology, Academic Medical Center, 1100 DD Amsterdam, The Netherlands
11Molecular Epidemiology Section, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
12The Netherlands Consortium for Healthy Ageing, 2300 RC Leiden, The Netherlands
13The Durrer Center for Cardiogenetic Research, 1105 AZ Amsterdam, The Netherlands

Received 25 November 2010; Revised 28 April 2011; Accepted 6 May 2011

Academic Editor: Anna Bersano

Copyright © 2011 Stella Trompet et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Introduction. The FSAP-Marburg I polymorphism (1704G > A), which reduces FSAP activity, is associated with late complications of carotid stenosis in humans. Therefore, this study examines the influence of the Marburg I polymorphism and the closely linked Marburg II polymorphism (1280G > C) on various cardiovascular outcomes in two large independent study populations. Methods. The two Marburg polymorphisms in the HABP2 gene encoding FSAP were genotyped in a large population of elderly patients at risk for vascular disease (the PROSPER-study, ) and in a study population treated with a percutaneous coronary intervention (the GENDER-study, ). Results. In the PROSPER study, the Marburg I polymorphism was associated with an increased risk of clinical stroke (HR: 1.60, 95% CI: 1.13–2.28) and all-cause mortality (HR: 1.33, 95% CI: 1.04–1.71). In the GENDER study carriers of this variant seemed at lower risk of developing restenosis (HR: 0.59, 95% CI: 0.34–1.01). The Marburg II polymorphism showed similar but weaker results. Conclusion. The increase in stroke risk in Marburg I carriers could be due to differential effects on smooth muscle cells and on matrix metalloproteinases, thereby influencing plaque stability. The possible protective effect on restenosis could be the result of reduced activation of zymogens, which are involved in hemostasis and matrix remodeling.