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

Overview

Journal Stroke Res Treat

Publisher Wiley

Date 2011 Jul 27

PMID 21789270

Citations 17

Authors

Stella Trompet

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

Rene A Tio

Robbert J de Winter

P Eline Slagboom

Rudi G J Westendorp

J Wouter Jukema

Affiliations

Soon will be listed here.

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.

Citing Articles

FSAP Protects against Histone-Mediated Increase in Endothelial Permeability In Vitro.

Cui X, Stavik B, Thiede B, Sandset P, Kanse S Int J Mol Sci. 2022; 23(22).

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Identification of a Phage Display-Derived Peptide Interacting with the N-Terminal Region of Factor VII Activating Protease (FSAP) Enables Characterization of Zymogen Activation.

Berge-Seidl S, Nielsen N, Rodriguez Alfonso A, Etscheid M, Kandanur S, Haug B ACS Chem Biol. 2022; 17(9):2631-2642.

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New Drug Targets to Prevent Death Due to Stroke: A Review Based on Results of Protein-Protein Interaction Network, Enrichment, and Annotation Analyses.

Maes M, Nikiforov N, Plaimas K, Suratanee A, Alfieri D, Reiche E Int J Mol Sci. 2021; 22(22).

PMID: 34829993 PMC: 8619767. DOI: 10.3390/ijms222212108.

Factor VII Activating Protease Expression in Human Platelets and Accumulation in Symptomatic Carotid Plaque.

Parahuleva M, Worsch M, Euler G, Choukeir M, Mardini A, Parviz B J Am Heart Assoc. 2020; 9(17):e016445.

PMID: 32856552 PMC: 7660758. DOI: 10.1161/JAHA.120.016445.

Design and Characterization of a New pVII Combinatorial Phage Display Peptide Library for Protease Substrate Mining Using Factor VII Activating Protease (FSAP) as Model.

Kara E, Nielsen N, Eggertsdottir B, Thiede B, Kanse S, Loset G Chembiochem. 2020; 21(13):1875-1884.

PMID: 32180321 PMC: 7383712. DOI: 10.1002/cbic.201900705.

References

Kannemeier C, Al-Fakhri N, Preissner K, Kanse S . Factor VII-activating protease (FSAP) inhibits growth factor-mediated cell proliferation and migration of vascular smooth muscle cells. FASEB J. 2004; 18(6):728-30. DOI: 10.1096/fj.03-0898fje. View

Shepherd J, Blauw G, Murphy M, Cobbe S, Bollen E, Buckley B . The design of a prospective study of Pravastatin in the Elderly at Risk (PROSPER). PROSPER Study Group. PROspective Study of Pravastatin in the Elderly at Risk. Am J Cardiol. 1999; 84(10):1192-7. DOI: 10.1016/s0002-9149(99)00533-0. View

Ikram M, Seshadri S, Bis J, Fornage M, DeStefano A, Aulchenko Y . Genomewide association studies of stroke. N Engl J Med. 2009; 360(17):1718-28. PMC: 2768348. DOI: 10.1056/NEJMoa0900094. View

Roemisch J, Feussner A, Nerlich C, Weimer T . The frequent Marburg I polymorphism impairs the pro-urokinase activating potency of the factor VII activating protease (FSAP). Blood Coagul Fibrinolysis. 2002; 13(5):433-41. DOI: 10.1097/00001721-200207000-00008. View

Ireland H, Miller G, Webb K, Cooper J, Humphries S . The factor VII activating protease G511E (Marburg) variant and cardiovascular risk. Thromb Haemost. 2004; 92(5):986-92. DOI: 10.1160/TH04-05-0275. View

Shepherd J, Blauw G, Murphy M, Bollen E, Buckley B, Cobbe S . Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002; 360(9346):1623-30. DOI: 10.1016/s0140-6736(02)11600-x. View

Hoppe B, Tolou F, Radtke H, Kiesewetter H, Dorner T, Salama A . Marburg I polymorphism of factor VII-activating protease is associated with idiopathic venous thromboembolism. Blood. 2004; 105(4):1549-51. DOI: 10.1182/blood-2004-08-3328. View

van Minkelen R, de Visser M, Vos H, Bertina R, Rosendaal F . The Marburg I polymorphism of factor VII-activating protease is not associated with venous thrombosis. Blood. 2005; 105(12):4898. DOI: 10.1182/blood-2005-02-0576. View

Sagui E, Mbaye P, Dubecq C, Ba Fall K, Niang A, Gning S . Ischemic and hemorrhagic strokes in Dakar, Senegal: a hospital-based study. Stroke. 2005; 36(9):1844-7. DOI: 10.1161/01.STR.0000177864.08516.47. View

10.

Agema W, Monraats P, Zwinderman A, de Winter R, Tio R, Doevendans P . Current PTCA practice and clinical outcomes in The Netherlands: the real world in the pre-drug-eluting stent era. Eur Heart J. 2004; 25(13):1163-70. DOI: 10.1016/j.ehj.2004.05.006. View

11.

Gulesserian T, Hron G, Endler G, Eichinger S, Wagner O, Kyrle P . Marburg I polymorphism of factor VII-activating protease and risk of recurrent venous thromboembolism. Thromb Haemost. 2006; 95(1):65-7. View

12.

Sedding D, Daniel J, Muhl L, Hersemeyer K, Brunsch H, Kemkes-Matthes B . The G534E polymorphism of the gene encoding the factor VII-activating protease is associated with cardiovascular risk due to increased neointima formation. J Exp Med. 2006; 203(13):2801-7. PMC: 2118185. DOI: 10.1084/jem.20052546. View

13.

Romisch J, Feussner A, Vermohlen S, Stohr H . A protease isolated from human plasma activating factor VII independent of tissue factor. Blood Coagul Fibrinolysis. 2000; 10(8):471-9. View

14.

Hoppe B, Tolou F, Dorner T, Kiesewetter H, Salama A . Gene polymorphisms implicated in influencing susceptibility to venous and arterial thromboembolism: frequency distribution in a healthy German population. Thromb Haemost. 2006; 96(4):465-70. View

15.

Romisch J, Vermohlen S, Feussner A, Stohr H . The FVII activating protease cleaves single-chain plasminogen activators. Haemostasis. 2000; 29(5):292-9. DOI: 10.1159/000022515. View

16.

Kanse S, Parahuleva M, Muhl L, Kemkes-Matthes B, Sedding D, Preissner K . Factor VII-activating protease (FSAP): vascular functions and role in atherosclerosis. Thromb Haemost. 2008; 99(2):286-9. DOI: 10.1160/TH07-10-0640. View

17.

Parahuleva M, Kanse S, Parviz B, Barth A, Tillmanns H, Bohle R . Factor Seven Activating Protease (FSAP) expression in human monocytes and accumulation in unstable coronary atherosclerotic plaques. Atherosclerosis. 2007; 196(1):164-171. DOI: 10.1016/j.atherosclerosis.2007.03.042. View

18.

Melcon C, Melcon M . Prevalence of stroke in an Argentine community. Neuroepidemiology. 2006; 27(2):81-8. DOI: 10.1159/000094978. View

19.

Willeit J, Kiechl S, Weimer T, Mair A, Santer P, Wiedermann C . Marburg I polymorphism of factor VII--activating protease: a prominent risk predictor of carotid stenosis. Circulation. 2003; 107(5):667-70. DOI: 10.1161/01.cir.0000055189.18831.b1. View