Lipoprotein Lipase Gene Polymorphisms and the Risk of Target Vessel Revascularization After Percutaneous Coronary Intervention

• Published in: Journal of the American College of Cardiology 2005-09, Vol.46 (6), p.1093-1100
• Main Authors: Monraats, Pascalle S., Rana, Jamal S., Nierman, Melchior C., Pires, Nuno M.M., Zwinderman, Aeilko H., Kastelein, John J.P., Kuivenhoven, Jan Albert, de Maat, Moniek P.M., Rittersma, Saskia Z.H., Schepers, Abbey, Doevendans, Pieter A.F., de Winter, Robbert J., Tio, René A., Frants, Rune R., Quax, Paul H.A., van Der Laarse, Arnoud, van Der Wall, Ernst E., Jukema, J. Wouter
• Format: Article
• Language: English
• Subjects: Angioplasty; Angioplasty, Balloon, Coronary; Biological and medical sciences; Cardiology; Cardiology. Vascular system; Cholesterol; Coronary Restenosis - genetics; Coronary vessels; Female; Heart attacks; Humans; Lipoprotein Lipase - genetics; Male; Medical sciences; Middle Aged; Polymorphism, Genetic; Risk Factors; Stents
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2005.05.071

Lipoprotein Lipase Gene Polymorphisms and the Risk of Target Vessel Revascularization After Percutaneous Coronary Intervention Pascalle S. Monraats, Jamal S. Rana, Melchior C. Nierman, Nuno M. M. Pires, Aeilko H. Zwinderman, John J. P. Kastelein, Jan Albert Kuivenhoven, Moniek P. M. de Maat, Saskia Z. H. Rittersma, Abbey Schepers, Pieter A. F. Doevendans, Robbert J. de Winter, Rene A. Tio, Rune R. Frants, Paul H. A. Quax, Arnoud van Der Laarse, Ernst E. van Der Wall, J. Wouter Jukema Genetic factors are important in the restenotic process after percutaneous coronary intervention (PCI). Therefore, we examined the impact of lipoprotein lipase (LPL) gene polymorphisms on restenosis, defined by target vessel revascularization (TVR) in a large patient population undergoing successful PCI. Systematic genotyping of four polymorphisms in the LPL gene was performed. The role of LPL in restenosis was also assessed in apolipoprotein E (ApoE)*3-Leiden transgenic mice. Carriers of the 447Ter allele of the LPL enzyme showed a lower risk of TVR compared with 447Ser homozygotes (p = 0.005). In the mouse model, LPL messenger ribonucleic acid levels increased 40-fold compared with control arteries. Clinical and animal data indicate that LPL plays a role in restenosis. We sought to identify polymorphisms in genes that predispose to restenosis. Variations in the lipoprotein lipase (LPL) gene have been implicated in a number of pathophysiologic conditions associated with coronary heart disease. The present study examines the impact of polymorphisms in the LPL gene on restenosis (defined by target vessel revascularization [TVR]) in a large patient population undergoing percutaneous coronary intervention (PCI). A mouse model for restenosis was used to further investigate LPL’s role in restenosis. The GENetic DEterminants of Restenosis (GENDER) project is a multicenter, prospective study design that enrolled 3,104 consecutive patients after successful PCI. These patients were genotyped for four different LPL gene polymorphisms. In apolipoprotein E (ApoE)*3-Leiden transgenic mice, arterial messenger ribonucleic acid (mRNA) was used to assess LPL expression during a cuff-induced restenotic process. Using multivariable analysis, carriers of the 447Ter allele of the LPL enzyme showed a lower risk of TVR compared with 447Ser homozygotes (p = 0.005). In the mouse model, LPL mRNA levels were increased 40-fold compared with control arteries at 6 h after cuff placement. The LPL C/G polymo