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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 
 AMERICAN JOURNAL OF CARDIOLOGY, Vol.104(1) : 46-51, 2009 
Journal Title
Issue Date
Angioplasty, Balloon, Coronary ; Aryl Hydrocarbon Hydroxylases/genetics* ; Confidence Intervals ; Coronary Artery Disease/drug therapy* ; Coronary Artery Disease/epidemiology ; Coronary Artery Disease/genetics ; Coronary Artery Disease/physiopathology ; Coronary Artery Disease/therapy ; Cytochrome P-450 CYP2C19 ; Drug Resistance/genetics* ; Female ; Humans ; Korea/epidemiology ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Platelet Aggregation Inhibitors/pharmacology ; Platelet Aggregation Inhibitors/therapeutic use* ; Polymorphism, Genetic* ; Polymorphism, Single Nucleotide ; Tetrazoles/pharmacology ; Tetrazoles/therapeutic use ; Ticlopidine/analogs & derivatives* ; Ticlopidine/pharmacology ; Ticlopidine/therapeutic use
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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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Ko, Young Guk(고영국) ORCID logo https://orcid.org/0000-0001-7748-5788
Kim, Jung Sun(김중선) ORCID logo https://orcid.org/0000-0003-2263-3274
Park, Sung Ha(박성하) ORCID logo https://orcid.org/0000-0001-5362-478X
Shim, Chi Young(심지영) ORCID logo https://orcid.org/0000-0002-6136-0136
Lee, Jung Myung(이정명)
Jang, Yang Soo(장양수) ORCID logo https://orcid.org/0000-0002-2169-3112
Choi, Dong Hoon(최동훈) ORCID logo https://orcid.org/0000-0002-2009-9760
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