TY - JOUR
T1 - Factor VII activating protease polymorphism (G534E) is associated with increased risk for stroke and mortality
AU - Trompet, Stella
AU - Pons, Douwe
AU - Kanse, Sandip M.
AU - De Craen, Anton J.M.
AU - Ikram, M. Arfan
AU - Verschuren, Jeffrey J.W.
AU - Zwinderman, Aeilko H.
AU - Doevendans, Pieter A.F.M.
AU - Tio, René A.
AU - De Winter, Robbert J.
AU - Slagboom, P. Eline
AU - Westendorp, Rudi G.J.
AU - Jukema, J. Wouter
PY - 2011
Y1 - 2011
N2 - Introduction: The FSAP-Marburg I polymorphism (1704GA), 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 (1280GC) 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.
AB - Introduction: The FSAP-Marburg I polymorphism (1704GA), 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 (1280GC) 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.
UR - http://www.scopus.com/inward/record.url?scp=80052452290&partnerID=8YFLogxK
U2 - 10.4061/2011/424759
DO - 10.4061/2011/424759
M3 - Article
AN - SCOPUS:80052452290
SN - 2090-8105
JO - Stroke Research and Treatment
JF - Stroke Research and Treatment
M1 - 424759
ER -