CES1A -816C as a Genetic Marker to Predict Greater Platelet Clopidogrel Response in Patients with Percutaneous Coronary Intervention

被引:32
作者
Zou, Jian-Jun [1 ,2 ]
Chen, Shao-Liang [2 ]
Fan, Hong-Wei [1 ]
Tan, Jie [1 ]
He, Bang-Shun [3 ]
Xie, Hong-Guang [1 ,3 ,4 ]
机构
[1] Nanjing Med Univ, Div Clin Pharmacol, Gen Clin Res Ctr, Nanjing Hosp 1, Nanjing 210006, Jiangsu, Peoples R China
[2] Nanjing Med Univ, Div Cardiovasc Med, Dept Med, Nanjing Heart Ctr,Nanjing Hosp 1, Nanjing 210006, Jiangsu, Peoples R China
[3] Nanjing Med Univ, Cent Lab, Gen Clin Res Ctr, Nanjing Hosp 1, Nanjing 210006, Jiangsu, Peoples R China
[4] Nanjing Med Univ, Dept Pharmacol, Sch Pharm, Nanjing 210006, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
CARBOXYLESTERASE; 1; PRODRUG OSELTAMIVIR; POLYMORPHISM; PHARMACOKINETICS; RESPONSIVENESS; ACTIVATION; VARIANTS; METABOLISM; IRINOTECAN; CLONING;
D O I
10.1097/FJC.0000000000000037
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
ABSTRACT:: This study was designed to determine whether CES1A -816A/C polymorphism could be associated with altered clopidogrel response. Recruited patients were pretreated with 300 mg clopidogrel loading dose before undergoing percutaneous coronary intervention for stenting and genotyped with CYP2C19 *2, *3, or *17, and CES1A -816A/C, respectively. Adenosine diphosphate-induced maximum platelet aggregation (MPA) was determined on day 3 after initiation of daily clopidogrel maintenance doses. The clinical primary end point was the 1-year incidence of definite stent thrombosis (ST). Multivariable linear regression revealed that the CES1A -816A/C polymorphism was independently associated with MPA measures with an absolute β value of 6.76. Of 617 patients, a subcohort of 249 patients not carrying CYP2C19 *2, *3, or *17 were categorized into 3 groups based on the -816A/C genotype. The median MPA value was lower in 125 carriers of the -816C variant than in 124 noncarriers (21.5% vs. 31.7%, P = 0.001). The 1-year definite ST occurred in 7 patients in that subcohort, and only 1 ST case was one of carriers of the -816 A/A that was associated with higher MPA values. The CES1A -816C would be used to predict greater platelet response to clopidogrel than the CES1A -816A in percutaneous coronary intervention-treated patients not carrying CYP2C19 variants. Copyright © 2013 by Lippincott Williams & Wilkins.
引用
收藏
页码:178 / 183
页数:6
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