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

Zou, Jian-Jun PhD*,†; Chen, Shao-Liang MD, PhD; Fan, Hong-Wei PhD*; Tan, Jie BS*; He, Bang-Shun MS; Xie, Hong-Guang MD, PhD*,‡,§

Journal of Cardiovascular Pharmacology:
doi: 10.1097/FJC.0000000000000037
Original Article
Abstract

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.

Author Information

*Division of Clinical Pharmacology, General Clinical Research Center;

Division of Cardiovascular Medicine, Department of Medicine, Nanjing Heart Center; and

Central Laboratory, General Clinical Research Center, Nanjing Medical University Nanjing First Hospital, Nanjing, China; and

§Department of Pharmacology, Nanjing Medical University School of Pharmacy, Nanjing, China.

Reprints: Hong-Guang Xie, MD, PhD, Division of Clinical Pharmacology, General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, 68 Changle Rd, Nanjing 210006, China (e-mail: hongg.xie@gmail.com); Shao-Liang Chen, MD, PhD, Division of Cardiovascular Medicine, Department of Medicine, and Nanjing Heart Center, Nanjing First Hospital, Nanjing Medical University, 68 Changle Rd, Nanjing 210006, China (e-mail: chmengx@126.com).

Supported in part by a grant (No. BK 2012525) funded by the Jiangsu Natural Science Foundation (JSNSF) and a grant (No. 2012-258) from the Ministry of Human Resource and Social Security, China (both to H.-G.X), and also by the National Natural Science Foundation of China grant (No. 30901830), Nanjing Bureau of Science and Technology (No. 201001098), and Nanjing Bureau of Health (No. QYK10142 and QYK11168) (to J.-J.Z).

J.-J. Zou participated in study design, conducted experiments, participated in data collection and statistical analysis, and drafted the Methods and Results sections. S.-L. Chen organized and supervised this clinical cohort study, and participated in study design, patient recruitment, data collection, and review of the data. H.-W. Fan, J. Tan, and B.-S. He analyzed the data. H.-G. Xie proposed the working hypothesis, designed the study, interpreted results, and wrote most of the article and finalized the whole revised version of the article. All authors approved the submitted version of the article.

The authors report no conflicts of interest.

Received August 12, 2013

Accepted October 21, 2013

© 2014 by Lippincott Williams & Wilkins.