|
|
Correlation between clopidogrel low response and CYP2C19 gene polymorphism in CAD patients after PCI |
SUN Yaqin1,2, YANG Shengli2, YANG Yong2 |
1.Xinxiang Medical University,Xinxiang 453003, China; 2.Department of Cardiology,the General Hospital of Chiense People’s Armed Police Forces, 100039 Beijing, China |
|
|
Abstract Objective To study the correlation between clopidogrel low respone and CYP2C19 gene polymorphism in coronary artery disease(CAD)patients after percutaneous coronary intervention(PCI). Methods A total of 200 patients with CAD admitted to this hospital from October 2013 to October 2014 were included in this study, and treated with dual antiplatelet drugs, aspirin and clopidogrel after PCI. The clopidogrel response was judged by depending on the ADP-induced platelet inhibition rate tested by thromboelastogram (TEG). In this study the ADP-induced platelet inhibition rate less than 30% was defined as clopidogrel low respone and the gene chip detection technology was used to detect the genotyes of CYP2C19 to further explore its effect on clopidogrel respone. Results In these 200 patients, the ADP-induced platelet inhibition rate was statistically significantly different between patients carrying CYP2C19*1/*1 and CYP2C19*1/*2、CYP2C19*1/*1 and CYP2C19*2/*2、extensive and intermediate metabolizers. The total occurrence of clopidogrel low response was 39.5%(79 patients) . There was significant difference between clopidogrel low respone and CYP2C19 genotyes、 metabolizers, indicating that more carriers with extensive metabolizer (CYP2C19*1/*1) in the clopidogrel response group(P=0.013), more carriers with intermediate or poor metabolizers in the clopidogrel low response group(P=0.013). Conclusions There is correlation between clopidogrel low respone and CYP2C19 gene polymorphism in patients with CAD after PCI, more carriers with intermediate or poor metabolizers in the clopidogrel low response group.
|
Received: 10 February 2015
|
|
|
|
|
[2] |
Kazui M, Nishiya Y, Ishizuka T, et al. Identification of the human cytochrome p450 enzymes involved in the two oxidative steps in the bioactivation of clopidogrel to its pharmacologically active metabolite[J]. Drug Metab Dispos,2010,38(1):92-99
|
[1] |
Shanker J, Gasparyan A Y, Kitas GD, et al. Platelet function and antiplatelet therapy in cardiovascular disease: implications of genetic polymorphisms[J]. Curr Vasc Pharmacol,2011,9(4):479-489.
|
[3] |
Bliden K P, Dichiara J, Tantry U S,et al. Increased risk in patients with high platelet aggregation receiving chronic clopidogrel therapy undergoing percutaneous coronary intervention: is the current antiplatelet therapy adequate [J].J Am Coll Cardiol, 2007,49(6):657-666.
|
[2] |
Kazui M, Nishiya Y, Ishizuka T, et al. Identification of the human cytochrome p450 enzymes involved in the two oxidative steps in the bioactivation of clopidogrel to its pharmacologically active metabolite[J]. Drug Metab Dispos,2010,38(1):92-99
|
[4] |
Caprie Steering, Committee. A randomized, blinded, trial of clopidogrel verse aspirin in patients at risk for ischemic events (CAPRIE) [J]. Lancet, 1996,348(9038):1329-1339.
|
[3] |
Bliden K P, Dichiara J, Tantry U S,et al. Increased risk in patients with high platelet aggregation receiving chronic clopidogrel therapy undergoing percutaneous coronary intervention: is the current antiplatelet therapy adequate [J].J Am Coll Cardiol, 2007,49(6):657-666.
|
[5] |
Mehta S R, Yusuf S. The clopidogrel in unstable angina to prevent recurrent events (cure) trial programme; rationale, design and baseline characteristics including a meta-analysis of the effects of pyridines in vascular disease[J]. Eur Heart J, 2000,21(24):2033-2041.
|
[4] |
Caprie Steering, Committee. A randomized, blinded, trial of clopidogrel verse aspirin in patients at risk for ischemic events (CAPRIE) [J]. Lancet, 1996,348(9038):1329-1339.
|
[6] |
Edwards J, Goodman S G, Yan R T ,et al. has the clopidogrel and metoprolol in myocardial infarction trial (commit) of early beta-blocker use in acute coronary syndromes impacted on clinical practice in canada [J].Am Heart J,2011,161(2):291-297.
|
[5] |
Mehta S R, Yusuf S. The clopidogrel in unstable angina to prevent recurrent events (cure) trial programme; rationale, design and baseline characteristics including a meta-analysis of the effects of pyridines in vascular disease[J]. Eur Heart J, 2000,21(24):2033-2041.
|
[6] |
Edwards J, Goodman S G, Yan R T ,et al. has the clopidogrel and metoprolol in myocardial infarction trial (commit) of early beta-blocker use in acute coronary syndromes impacted on clinical practice in canada [J].Am Heart J,2011,161(2):291-297.
|
[7] |
韩雅玲.冠心病抗血小板治疗[J]. 武警医学, 2006,17(3):163-166.
|
[7] |
韩雅玲.冠心病抗血小板治疗[J]. 武警医学, 2006,17(3):163-166.
|
[8] |
Hou X, Shi J, Sun H .Gene polymorphism of cytochrome P450 2C19*2 and clopidogrel resistance reflected by platelet function assays: a meta-analysis[J]. Eur J Clin Pharmacol,2014,70(9):1041-1047.
|
[8] |
Hou X, Shi J, Sun H .Gene polymorphism of cytochrome P450 2C19*2 and clopidogrel resistance reflected by platelet function assays: a meta-analysis[J]. Eur J Clin Pharmacol,2014,70(9):1041-1047.
|
[9] |
Zhang X, Yan L, Wang D, et al. Comparison of loading with maintenance dose of clopidogrel on platelet reactivity in Chinese with different CYP2C19 genotypes prior to percutaneous coronary intervention[J].Chin Med J (Engl),2014,123(14):2571-2577.
|
[9] |
Zhang X, Yan L, Wang D, et al. Comparison of loading with maintenance dose of clopidogrel on platelet reactivity in Chinese with different CYP2C19 genotypes prior to percutaneous coronary intervention[J].Chin Med J (Engl),2014,123(14):2571-2577.
|
[10] |
Vlachojannis G J, Dimitropoulos G, Alexopoulos D. Clopidogrel resistance: current aspects and future directions[J]. Hellenic J Cardiol, 2011, 52(3):236-245.
|
[10] |
Vlachojannis G J, Dimitropoulos G, Alexopoulos D. Clopidogrel resistance: current aspects and future directions[J]. Hellenic J Cardiol, 2011, 52(3):236-245.
|
[11] |
Frere C, Cuisset T, Morange P E, et al. Effect of cytochrome p45.00 polymorphisms on platelet reactivity after treatment with clopidogrel in acute coronary syndrome[J].Am J Cardiol, 2008,101(8):1088-1093.
|
[11] |
Frere C, Cuisset T, Morange P E, et al. Effect of cytochrome p45.00 polymorphisms on platelet reactivity after treatment with clopidogrel in acute coronary syndrome[J].Am J Cardiol, 2008,101(8):1088-1093.
|
[12] |
Hokimoto S, Mizobe M, Akasaka T, et al. Impact of CYP2C19 polymorphism and proton pump inhibitors on platelet reactivity to clopidogrel and clinical outcomes following stent implantation[J]. Thromb Res,2014,133(4):599-605.
|
[12] |
Hokimoto S, Mizobe M, Akasaka T, et al. Impact of CYP2C19 polymorphism and proton pump inhibitors on platelet reactivity to clopidogrel and clinical outcomes following stent implantation[J]. Thromb Res,2014,133(4):599-605.
|
[13] |
Collet J P, Hulot J S, Anzaha G, et al. High doses of clopidogrel to overcome genetic resistance: the randomized crossover CLOVIS-2 (Clopidogrel and Response Variability Investigation Study2)[J]. JACC Cardiovasc Interv,2011,4(4):392-402.
|
[13] |
Collet J P, Hulot J S, Anzaha G, et al. High doses of clopidogrel to overcome genetic resistance: the randomized crossover CLOVIS-2 (Clopidogrel and Response Variability Investigation Study2)[J]. JACC Cardiovasc Interv,2011,4(4):392-402.
|
[14] |
Mega J L, Hochholzer W, Frelinger A L , et al. Dosing clopidogrel based on CYP2C19 genotype and the effect on platelet reactivity in patients with stable cardiovascular disease[J]. JAMA,2011,306(20):2221-2228.
|
[14] |
Mega J L, Hochholzer W, Frelinger A L , et al. Dosing clopidogrel based on CYP2C19 genotype and the effect on platelet reactivity in patients with stable cardiovascular disease[J]. JAMA,2011,306(20):2221-2228.
|
[1] |
YANG Yong, MENG Taojing, MA Dongxin, LIU Ying, SHEN Zhiqi, HUANG Jie, ZHAO Qing, WANG Ranran, and YANG Changchun. Relationships between TREM-1 gene polymorphism and susceptibility to male premature coronary artery disease[J]. Med. J. Chin. Peop. Armed Poli. Forc., 2019, 30(2): 97-100. |
|
|
|
|