Effect of carboxylesterase 1 S75N on clopidogrel therapy among acute coronary syndrome patients

Fei-Yan Xiao; Jian-Quan Luo; Min Liu; Bi-Lian Chen; Shan Cao; Zhao-Qian Liu; Hong-Hao Zhou; Gan Zhou; Wei Zhang

doi:10.1038/s41598-017-07736-1

Effect of carboxylesterase 1 S75N on clopidogrel therapy among acute coronary syndrome patients

Sci Rep. 2017 Aug 3;7(1):7244. doi: 10.1038/s41598-017-07736-1.

Authors

Fei-Yan Xiao^{1

2}, Jian-Quan Luo^{1

2}, Min Liu³, Bi-Lian Chen⁴, Shan Cao^{1

2}, Zhao-Qian Liu^{1

2}, Hong-Hao Zhou^{1

2}, Gan Zhou^{5

6

7}, Wei Zhang^{8

9}

Affiliations

¹ Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, China.
² Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha, China.
³ Department of cardiovascular, Zhengzhou central hospital, Zhengzhou University, Zhengzhou, China.
⁴ Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, China.
⁵ Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, China. [email protected].
⁶ Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha, China. [email protected].
⁷ National institution of drug clinical trial, Xiangya Hospital, Central South University, Changsha, China. [email protected].
⁸ Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, China. [email protected].
⁹ Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha, China. [email protected].

Abstract

Carboxylesterase 1 (CES1) hydrolyzes the prodrug clopidogrel to an inactive carboxylic acid metabolite. The effects of CES1 S75N (rs2307240,C>T) on clopidogrel response among 851 acute coronary syndrome patients who came from the north, central and south of China were studied. The occurrence ratios of each endpoint in the CC group were significantly higher than in the CT + TT group for cerebrovascular events (14% vs 4.8%, p < 0.001, OR = 0.31), acute myocardial infarction (15.1% vs 6.1%, p < 0.001, OR = 0.37) and unstable angina (62.8% vs 37.7%, p < 0.001, OR = 0.36). The results showed that there was a significant association between CES1 S75N (rs2307240) and the outcome of clopidogrel therapy. Moreover, the frequency of the T allele of rs2307240 in acute coronary syndrome patients (MAF = 0.22) was more than four times higher than that in the general public (MAF = 0.05).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acute Coronary Syndrome / drug therapy*
Acute Coronary Syndrome / genetics*
Aged
Alleles*
Amino Acid Substitution
Carboxylic Ester Hydrolases / genetics*
Clopidogrel / pharmacology
Clopidogrel / therapeutic use*
Comorbidity
Female
Gene Frequency
Genotype
Humans
Male
Middle Aged
Pharmacogenomic Variants
Platelet Aggregation Inhibitors / pharmacology
Platelet Aggregation Inhibitors / therapeutic use
Polymorphism, Single Nucleotide*
Purinergic P2Y Receptor Antagonists / pharmacology
Purinergic P2Y Receptor Antagonists / therapeutic use
Treatment Outcome

Substances

Platelet Aggregation Inhibitors
Purinergic P2Y Receptor Antagonists
Clopidogrel
Carboxylic Ester Hydrolases
CES1 protein, human