Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011:2011:424759.
doi: 10.4061/2011/424759. Epub 2011 Jun 30.

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

Stella Trompet  1 , Douwe Pons, Sandip M Kanse, Anton J M de Craen, M Arfan Ikram, Jeffrey J W Verschuren, Aeilko H Zwinderman, Pieter A F M Doevendans, René A Tio, Robbert J de Winter, P Eline Slagboom, Rudi G J Westendorp, J Wouter Jukema
Affiliations

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

Stella Trompet et al. Stroke Res Treat. 2011.

Abstract

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, n = 5804) and in a study population treated with a percutaneous coronary intervention (the GENDER-study, n = 3104). 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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Marburg I hazard ratios for vascular endpoints in GENDER and PROSPER. The Marburg I (G534E) polymorphism is associated with an increased risk for stroke and mortality in the PROSPER study, whereas it tends to reduce the risk for clinical restenosis in the GENDER study.
Figure 2
Figure 2
Marburg II hazard ratios for vascular endpoints in GENDER and PROSPER. As the Marburg II polymorphism does not lead to altered enzymatic activity, the similar trends that were observed for this variant are probably a result of the high linkage disequilibrium between the Marburg variants. Despite high confidence intervals, a significant effect was observed on mortality.
See this image and copyright information in PMC

References

    1. Römisch J, Feußner A, Vermöhlen S, Stöhr HA. A protease isolated from human plasma activating factor vii independent of tissue factor. Blood Coagulation and Fibrinolysis. 1999;10(8):471–479. - PubMed
    1. Römisch J, Vermöhlen S, Feussner A, Stöhr HA. The FVII activating protease cleaves single-chain plasminogen activators. Haemostasis. 2000;29(5):292–299. - PubMed
    1. Roemisch J, Feussner A, Nerlich C, Stoehr HA, Weimer T. The frequent Marburg I polymorphism impairs the pro-urokinase activating potency of the factor VII activating protease (FSAP) Blood Coagulation and Fibrinolysis. 2002;13(5):433–441. - PubMed
    1. Gulesserian T, Hron G, Endler G, Eichinger S, Wagner O, Kyrle PA. Marburg I polymorphism for factor VII-activating protease and risk of recurrent venous thromboembolism. Thrombosis and Haemostasis. 2006;95(1):65–67. - PubMed
    1. Hoppe B, Tolou F, Radtke H, Kiesewetter H, Dörner T, Salama A. Marburg I polymorphism of factor VII-activating protease is associated with idiopathic venous thromboembolism. Blood. 2005;105(4):1549–1551. - PubMed

LinkOut - more resources