title: Factor VII Activating Protease Polymorphism (G534E) Is Associated with Increased Risk for Stroke and Mortality.
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.
authors.affiliation: Department of Cardiology, Leiden University Medical Center, C5-P, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: Stella
authors.initials: S
authors.lastname: Trompet
authors.forename: Douwe
authors.initials: D
authors.lastname: Pons
authors.forename: Sandip M
authors.initials: SM
authors.lastname: Kanse
authors.forename: Anton J M
authors.initials: AJ
authors.lastname: de Craen
authors.forename: M Arfan
authors.initials: MA
authors.lastname: Ikram
authors.forename: Jeffrey J W
authors.initials: JJ
authors.lastname: Verschuren
authors.forename: Aeilko H
authors.initials: AH
authors.lastname: Zwinderman
authors.forename: Pieter A F M
authors.initials: PA
authors.lastname: Doevendans
authors.forename: René A
authors.initials: RA
authors.lastname: Tio
authors.forename: Robbert J
authors.initials: RJ
authors.lastname: de Winter
authors.forename: P Eline
authors.initials: PE
authors.lastname: Slagboom
authors.forename: Rudi G J
authors.initials: RG
authors.lastname: Westendorp
authors.forename: J Wouter
authors.initials: JW
authors.lastname: Jukema