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

Trompet S, Pons D, Kanse SM, de Craen AJ, Ikram MA, Verschuren JJ, Zwinderman AH, Doevendans PA, Tio RA, de Winter RJ, Slagboom PE, Westendorp RG, Jukema JW - Stroke Res Treat (2011)

Bottom Line: The Marburg II polymorphism showed similar but weaker results.Conclusion.The possible protective effect on restenosis could be the result of reduced activation of zymogens, which are involved in hemostasis and matrix remodeling.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Leiden University Medical Center, C5-P, P.O. Box 9600, 2300 RC Leiden, The Netherlands.

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.

No MeSH data available.


Related in: MedlinePlus

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.
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Related In: Results  -  Collection


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fig1: 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.

Mentions: Using a Cox proportional hazards model, which included the variables sex, age, pravastatin use, and country, a significant association was found between the Marburg I polymorphism and clinical stroke. Figure 1 shows that the combined group of heterozygotes (n = 518) and homozygotes (n = 17) was at increased risk for clinical stroke (HR: 1.6, 95% CI: 1.13–2.28, P = .009) when compared to the wild type group (n = 5162). Also, all-cause mortality was significantly higher in patients carrying one or two copies of this variant (HR: 1.33, 95% CI: 1.04–1.71, P = .025). The increased mortality was mainly a result of an increase in vascular mortality (HR: 1.37, 95% CI: 0.96–1.97, P = .082), whereas vascular mortality was mainly determined by death from stroke. The Marburg I polymorphism did not seem to influence the risk for coronary events (HR: 0.98, 95% CI: 0.75–1.29). Additional adjustment for traditional risk factors (hypertension, diabetes, smoking, and cholesterol levels) did not change the results (HR: 1.63, 95% CI: 1.14–2.31, P = .007).


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

Trompet S, Pons D, Kanse SM, de Craen AJ, Ikram MA, Verschuren JJ, Zwinderman AH, Doevendans PA, Tio RA, de Winter RJ, Slagboom PE, Westendorp RG, Jukema JW - Stroke Res Treat (2011)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3140705&req=5

fig1: 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.
Mentions: Using a Cox proportional hazards model, which included the variables sex, age, pravastatin use, and country, a significant association was found between the Marburg I polymorphism and clinical stroke. Figure 1 shows that the combined group of heterozygotes (n = 518) and homozygotes (n = 17) was at increased risk for clinical stroke (HR: 1.6, 95% CI: 1.13–2.28, P = .009) when compared to the wild type group (n = 5162). Also, all-cause mortality was significantly higher in patients carrying one or two copies of this variant (HR: 1.33, 95% CI: 1.04–1.71, P = .025). The increased mortality was mainly a result of an increase in vascular mortality (HR: 1.37, 95% CI: 0.96–1.97, P = .082), whereas vascular mortality was mainly determined by death from stroke. The Marburg I polymorphism did not seem to influence the risk for coronary events (HR: 0.98, 95% CI: 0.75–1.29). Additional adjustment for traditional risk factors (hypertension, diabetes, smoking, and cholesterol levels) did not change the results (HR: 1.63, 95% CI: 1.14–2.31, P = .007).

Bottom Line: The Marburg II polymorphism showed similar but weaker results.Conclusion.The possible protective effect on restenosis could be the result of reduced activation of zymogens, which are involved in hemostasis and matrix remodeling.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Leiden University Medical Center, C5-P, P.O. Box 9600, 2300 RC Leiden, The Netherlands.

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.

No MeSH data available.


Related in: MedlinePlus