TY - JOUR
T1 - The influence of established genetic variation in the haemostatic system on clinical restenosis after percutaneous coronary interventions
AU - Pons, Douwe
AU - Monraats, Pascalle S.
AU - de Maat, Moniek P. M.
AU - Pires, Nuno M. M.
AU - Quax, Paul H. A.
AU - van Vlijmen, Bart J. M.
AU - Rosendaal, Frits R.
AU - Zwinderman, Aeilko H.
AU - Doevendans, Pieter A. F. M.
AU - Waltenberger, Johannes
AU - de Winter, Robbert J.
AU - Tio, Rene A.
AU - Frants, Rune R.
AU - van der Laarse, Arnoud
AU - van der Wall, Ernst E.
AU - Jukema, J. Wouter
PY - 2007/12
Y1 - 2007/12
N2 - 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 11, Factor V, Factor VII and PAI- I genes. The PAI-I 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%Cl: 1.05-2.03), whereas patients with the 4G/4G genotype had an even further increased risk (HR: 1.69, 95%Cl: 1.19-2.41). In contrast, the factorV 506GIn (factor V Leiden) amino acid substitution was associated with a decreased risk ofTVR (HR: 0.41, 95%Cl: 0.19-0.86). Our findings indicate that polymorphisms in the factorV and PAI- I genes may play a role in the process of restenosis.
AB - 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 11, Factor V, Factor VII and PAI- I genes. The PAI-I 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%Cl: 1.05-2.03), whereas patients with the 4G/4G genotype had an even further increased risk (HR: 1.69, 95%Cl: 1.19-2.41). In contrast, the factorV 506GIn (factor V Leiden) amino acid substitution was associated with a decreased risk ofTVR (HR: 0.41, 95%Cl: 0.19-0.86). Our findings indicate that polymorphisms in the factorV and PAI- I genes may play a role in the process of restenosis.
KW - restenosis
KW - polymorphisms
KW - coagulation factors
KW - PLASMINOGEN-ACTIVATOR INHIBITOR-1
KW - FACTOR-V-LEIDEN
KW - STENT PLACEMENT
KW - PROTEIN-C
KW - PAI-I
KW - 4G/5G POLYMORPHISM
KW - ADIPOSE-TISSUE
KW - SEVERE SEPSIS
KW - PLASMA-LEVELS
KW - RISK
U2 - 10.1160/TH07-04-0301
DO - 10.1160/TH07-04-0301
M3 - Article
SN - 0340-6245
VL - 98
SP - 1323
EP - 1328
JO - Thrombosis and Haemostasis
JF - Thrombosis and Haemostasis
IS - 6
ER -