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The influence of established genetic variation in the haemostatic system on clinical restenosis after percutaneous coronary interventions

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
DOI: https://doi.org/10.1160/TH07-04-0301
Issue: 2007: 98/6 (Dec) pp. 1155-1391
Pages: 1323-1328

The influence of established genetic variation in the haemostatic system on clinical restenosis after percutaneous coronary interventions

Douwe Pons 1,2, Pascalle S. Monraats 1,2, Moniek P. M. de Maat 3, Nuno M. M. Pires1,4, Paul H. A. Quax4,5, Bart J. M. van Vlijmen 6, Frits R. Rosendaal 7, Aeilko H. Zwinderman 8, Pieter A. F. M. Doevendans 9, Johannes Waltenberger 10, Robbert J. de Winter 1 1, René A. Tio 12, Rune R. Frants 1 3, Arnoud van der Laarse 1, Ernst E. van der Wall 1, J. Wouter Jukema1,2
1 Department of Cardiology, Leiden University Medical Center, Leiden; 2 Interuniversity Cardiology Institute of the Netherlands (ICIN), Utrecht; 3 Department of Hematology, Erasmus University Medical Center, Rotterdam; 4 Gaubius Laboratory, TNO PG, Leiden; 5 Department of Surgery, Leiden University Medical Center, Leiden; 6 Department of Hematology, Leiden University Medical Center, Leiden; 7 Department of Clinical Epidemiology, Leiden University Medical Center, Leiden; 8 Department of Medical Statistics, Academic Medical Center, Amsterdam; 9 Department of Cardiology, University Medical Center Utrecht, Utrecht; 10 Department of Cardiology, Academic Hospital Maastricht, Maastricht; 11 Department of Cardiology, Academic Medical Center, Amsterdam; 12 Department of Cardiology, University Medical Center Groningen, Groningen; 13 Department of Human Genetics, Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden; The Netherlands

Keywords

Restenosis, polymorphisms, Coagulation factors

Summary

Since activation of the haemostatic system is an important feature of the wound healing response triggered by arterial injury, variations in genes involved in thrombus formation may play a role in restenosis after percutaneous coronary interventions (PCI). Therefore, our aim was to examine the relationship between polymorphisms that are known to play a role in the haemostatic system and the risk of clinical restenosis in the GENetic DEterminants of Restenosis (GENDER) study,a multicenter prospective study design that enrolled 3,104 consecutive patients after successful PCI.Target vessel revascularization (TVR) was the primary endpoint. All patients were genotyped for six polymorphisms in the Factor II, Factor V, Factor VII and PAI-1 genes. The PAI-1 4G variant was associated with an increased risk ofTVR.When compared to 5G/5G homozygotes, heterozygous patients were at higher risk for TVR (HR: 1.46, 95%CI: 1.05–2.03), whereas patients with the 4G/4G genotype had an even further increased risk (HR: 1.69, 95%CI: 1.19–2.41). In contrast, the factor V 506Gln (factor V Leiden) amino acid substitution was associated with a decreased risk of TVR (HR: 0.41, 95%CI: 0.19–0.86). Our findings indicate that polymorphisms in the factorV and PAI-1 genes may play a role in the process of restenosis.

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