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

Douwe Pons; Pascalle S. Monraats; Moniek P. M. de Maat; Nuno M. M. Pires; Paul H. A. Quax; Bart J. M. van Vlijmen; Frits R. Rosendaal; Aeilko H. Zwinderman; Pieter A. F. M. Doevendans; Johannes Waltenberger; Robbert J. de Winter; René A. Tio; Rune R. Frants; Arnoud van der Laarse; Ernst E. Vander Wall; Wouter J. Jukema

doi:10.1160/TH07-04-0301

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2007; 98(06): 1323-1328
DOI: 10.1160/TH07-04-0301

Cardiovascular Biology and Cell Signalling

Schattauer GmbH

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

Authors

Douwe Pons

¹Department of Cardiology, Leiden University Medical Center, Leiden

²Interuniversity Cardiology Institute of the Netherlands (ICIN), Utrecht
Pascalle S. Monraats

¹Department of Cardiology, Leiden University Medical Center, Leiden

²Interuniversity Cardiology Institute of the Netherlands (ICIN), Utrecht
Moniek P. M. de Maat

³Department of Hematology, Erasmus University Medical Center, Rotterdam
Nuno M. M. Pires

¹Department of Cardiology, Leiden University Medical Center, Leiden

⁴Gaubius Laboratory, TNO PG, Leiden
Paul H. A. Quax

⁴Gaubius Laboratory, TNO PG, Leiden

⁵Department of Surgery, Leiden University Medical Center, Leiden
Bart J. M. van Vlijmen

⁶Department of Hematology, Leiden University Medical Center, Leiden
Frits R. Rosendaal

⁷Department of Clinical Epidemiology, Leiden University Medical Center, Leiden
Aeilko H. Zwinderman

⁸Department of Medical Statistics, Academic Medical Center, Amsterdam
Pieter A. F. M. Doevendans

⁹Department of Cardiology, University Medical Center Utrecht, Utrecht
Johannes Waltenberger

¹⁰Department of Cardiology, Academic Hospital Maastricht, Maastricht
Robbert J. de Winter

¹¹Department of Cardiology, Academic Medical Center, Amsterdam
René A. Tio

¹²Department of Cardiology, University Medical Center Groningen, Groningen
Rune R. Frants

¹³Department of Human Genetics, Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden; The Netherlands
Arnoud van der Laarse

¹Department of Cardiology, Leiden University Medical Center, Leiden
Ernst E. Vander Wall

¹Department of Cardiology, Leiden University Medical Center, Leiden
Wouter J. Jukema

¹Department of Cardiology, Leiden University Medical Center, Leiden

²Interuniversity Cardiology Institute of the Netherlands (ICIN), Utrecht

Abstract

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.

Keywords

Restenosis - polymorphisms - coagulation factors

Full Text

References

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