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

Abstract

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 of TVR. 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.

• Authors: 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 van der Wall, J Wouter Jukema
• Journal: Thrombosis and haemostasis (Thromb Haemost) Vol. 98 Issue 6 Pg. 1323-8 (Dec 2007) ISSN: 0340-6245 [Print] Germany
• PMID: 18064331 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Plasminogen Activator Inhibitor 1
• SERPINE1 protein, human
• factor V Leiden
• Factor V
• Factor VII
• Prothrombin

Topics

• Aged
• Angioplasty, Balloon, Coronary (adverse effects)
• Coronary Restenosis (blood, genetics)
• Coronary Stenosis (genetics, therapy)
• Diabetes Complications (genetics)
• Factor V (genetics)
• Factor VII (genetics)
• Female
• Follow-Up Studies
• Genetic Predisposition to Disease
• Hemostasis (genetics)
• Heterozygote
• Homozygote
• Humans
• Male
• Middle Aged
• Netherlands
• Phenotype
• Plasminogen Activator Inhibitor 1 (genetics)
• Polymorphism, Genetic
• Proportional Hazards Models
• Prospective Studies
• Prothrombin (genetics)
• Research Design
• Risk Assessment
• Risk Factors
• Smoking (adverse effects)
• Time Factors
• Treatment Outcome