Relation of Genetic Polymorphisms in the Cytochrome P450 Gene With Clopidogrel Resistance After Drug-Eluting Stent Implantation in Koreans

Jung Myung Lee, Sungha Park, Dong Jik Shin, Donghoon Choi, Chi Young Shim, Young Guk Ko, Jung Sun Kim, Eun Soon Shin, Chong Won Chang, Jong Eun Lee, Yangsoo Jang

Research output: Contribution to journalArticle

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Abstract

Clopidogrel is a prodrug that has to be converted to an active metabolite by hepatic cytochrome P450 (CYP) isoenzymes to inhibit platelet aggregation. Individual variability of platelet inhibition by clopidogrel suggests a possibility for genetic factors having a significant influence on clopidogrel responsiveness. In this study, we sought to determine the relation of genetic polymorphisms of CYP genes to clopidogrel resistance in Koreans. Four hundred fifty patients who underwent successful percutaneous coronary intervention with drug-eluting stents were randomly assigned to treatment with dual antiplatelet regimen (aspirin plus clopidogrel) or triple antiplatelet regimen (aspirin plus clopidogrel plus cilostazol). Clopidogrel resistance using VerifyNow P2Y12 assay and genetic analysis were performed in 387 patients. Clopidogrel resistance was found in 112 patients (28.9%). In the clopidogrel-responsive group, there was a significantly higher proportion of cilostazol use. Because cilostazol showed a significant influence on clopidogrel resistance, we examined the association of single-nucleotide polymorphisms and clopidogrel resistance in the dual and triple antiplatelet therapy groups, respectively. In all subjects, the CYP2C19*3A allele was significantly more prevalent in the clopidogrel-resistant group compared with the clopidogrel-responsive group. Multiple logistic regression analysis demonstrated that CYP2C19*3 is an independent predictor of clopidogrel resistance. In conclusion, CYP2C19*3 single-nucleotide polymorphisms is an independent risk factor of clopidogrel resistance in Korean subjects with coronary artery disease.

Original languageEnglish
Pages (from-to)46-51
Number of pages6
JournalAmerican Journal of Cardiology
Volume104
Issue number1
DOIs
Publication statusPublished - 2009 Jul 1

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clopidogrel
Drug-Eluting Stents
Genetic Polymorphisms
Cytochrome P-450 Enzyme System
Genes
Aspirin
Single Nucleotide Polymorphism

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Lee, Jung Myung ; Park, Sungha ; Shin, Dong Jik ; Choi, Donghoon ; Shim, Chi Young ; Ko, Young Guk ; Kim, Jung Sun ; Shin, Eun Soon ; Chang, Chong Won ; Lee, Jong Eun ; Jang, Yangsoo. / Relation of Genetic Polymorphisms in the Cytochrome P450 Gene With Clopidogrel Resistance After Drug-Eluting Stent Implantation in Koreans. In: American Journal of Cardiology. 2009 ; Vol. 104, No. 1. pp. 46-51.
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abstract = "Clopidogrel is a prodrug that has to be converted to an active metabolite by hepatic cytochrome P450 (CYP) isoenzymes to inhibit platelet aggregation. Individual variability of platelet inhibition by clopidogrel suggests a possibility for genetic factors having a significant influence on clopidogrel responsiveness. In this study, we sought to determine the relation of genetic polymorphisms of CYP genes to clopidogrel resistance in Koreans. Four hundred fifty patients who underwent successful percutaneous coronary intervention with drug-eluting stents were randomly assigned to treatment with dual antiplatelet regimen (aspirin plus clopidogrel) or triple antiplatelet regimen (aspirin plus clopidogrel plus cilostazol). Clopidogrel resistance using VerifyNow P2Y12 assay and genetic analysis were performed in 387 patients. Clopidogrel resistance was found in 112 patients (28.9{\%}). In the clopidogrel-responsive group, there was a significantly higher proportion of cilostazol use. Because cilostazol showed a significant influence on clopidogrel resistance, we examined the association of single-nucleotide polymorphisms and clopidogrel resistance in the dual and triple antiplatelet therapy groups, respectively. In all subjects, the CYP2C19*3A allele was significantly more prevalent in the clopidogrel-resistant group compared with the clopidogrel-responsive group. Multiple logistic regression analysis demonstrated that CYP2C19*3 is an independent predictor of clopidogrel resistance. In conclusion, CYP2C19*3 single-nucleotide polymorphisms is an independent risk factor of clopidogrel resistance in Korean subjects with coronary artery disease.",
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Relation of Genetic Polymorphisms in the Cytochrome P450 Gene With Clopidogrel Resistance After Drug-Eluting Stent Implantation in Koreans. / Lee, Jung Myung; Park, Sungha; Shin, Dong Jik; Choi, Donghoon; Shim, Chi Young; Ko, Young Guk; Kim, Jung Sun; Shin, Eun Soon; Chang, Chong Won; Lee, Jong Eun; Jang, Yangsoo.

In: American Journal of Cardiology, Vol. 104, No. 1, 01.07.2009, p. 46-51.

Research output: Contribution to journalArticle

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