The influence of established genetic variation in the haemostatic system on clinical restenosis after percutaneous coronary interventions
Douwe Pons1,2, Pascalle S. Monraats1,2, Moniek P. M. de Maat3, Nuno M. M. Pires1,4, Paul H. A. Quax4,5, Bart J. M. van Vlijmen6, Frits R. Rosendaal7, Aeilko H. Zwinderman8, Pieter A. F. M. Doevendans9, Johannes Waltenberger10, Robbert J. de Winter11, René A. Tio12, Rune R. Frants13, Arnoud van der Laarse1, Ernst E. van der Wall1, J. Wouter Jukema1,2
1Department of Cardiology, Leiden University Medical Center, Leiden; 2Interuniversity Cardiology Institute of the Netherlands (ICIN), Utrecht; 3Department of Hematology, Erasmus University Medical Center, Rotterdam; 4Gaubius Laboratory, TNO PG, Leiden; 5Department of Surgery, Leiden University Medical Center, Leiden; 6Department of Hematology, Leiden University Medical Center, Leiden; 7Department of Clinical Epidemiology, Leiden University Medical Center, Leiden; 8Department of Medical Statistics, Academic Medical Center, Amsterdam; 9Department of Cardiology, University Medical Center Utrecht, Utrecht; 10Department of Cardiology, Academic Hospital Maastricht, Maastricht; 11Department of Cardiology, Academic Medical Center, Amsterdam; 12Department of Cardiology, University Medical Center Groningen, Groningen; 13Department of Human Genetics, Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden; The Netherlands
Restenosis, polymorphisms, Coagulation factors
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.