Genetic determinants of clopidogrel responsiveness in Koreans treated with drug-eluting stents

Park, Jin Joo; Park, Kyung Woo; Kang, Jeehoon; Jeon, Ki‐Hyun; Kang, Sang‐Won; Ahn, Hyun Young; Han, Jung‐Kyu; Koh, Jin‐Sin; Lee, Sang Eun; Yang, Han–Mo; Lee, Hae Young; Kang, Hyun–Jae; Koo, Bon‐Kwon; Oh, Byung‐Hee; Park, Young-Bae; Kim, Hyo–Soo

doi:10.1016/j.ijcard.2012.09.075

Cited by 29 publications

(36 citation statements)

References 40 publications

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“…Our results are in agreement with those reported by earlier studies. [29][30][31] Interestingly, no patient was wild type and heterozygous for CYP2C19 * 3. In addition, the number of heterozygous patients for CYP2C19 * 17 was also rare.…”

Section: Discussionmentioning

confidence: 99%

“…These results were consistent with several other reports from China and western countries. [31][32][33][34][35] The last genetic polymorphism that was evaluated in this study was glycoprotein IIIa (GPIIIa;1565T>C), which is part of the integrin complex present on platelets, and acts as a receptor for fibrinogen and von Willebrand factor that aids in platelet activation. Since genetic polymorphisms in the P2Y 12 receptor were not associated with HTPR, we sought to deter- 36) and Isordia-Salas.…”

Section: Discussionmentioning

confidence: 99%

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Genotype Frequencies of CYP2C19, P2Y<sub>12</sub> and GPIIIa Polymorphisms in Coronary Heart Disease Patients of Han Ethnicity, and Their Impact on Clopidogrel Responsiveness

et al. 2016

Int. Heart J.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Genotype Frequencies of CYP2C19, P2Y<sub>12</sub> and GPIIIa Polymorphisms in Coronary Heart Disease Patients of Han Ethnicity, and Their Impact on Clopidogrel Responsiveness

et al. 2016

Int. Heart J.

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“…However, the CYP1A2 , the CYP2B6 , the CYP3A4, and CYP3A5 did not have any effect. Park and colleagues indicated similar findings; however, they did not investigate the effect of CYP2C9 variants [37]. Although several studies showed that the CYP2B6 polymorphism did not have an effect, a study indicated that carriers of the CYP2B6 had lower exposure to clopidogrel active metabolite and lower platelets inhibition compared to noncarriers [34].…”

Section: Genetic Factors Contributing To Clopidogrel Htprmentioning

confidence: 99%

“…Although several studies showed that the CYP2B6 polymorphism did not have an effect, a study indicated that carriers of the CYP2B6 had lower exposure to clopidogrel active metabolite and lower platelets inhibition compared to noncarriers [34]. Although several studies suggested that the association between the CYP3A4 and the CYP3A5 polymorphisms and clopidogrel HTPR is not significant [34, 37–39], others indicated significant association between them [11, 20, 40]. This might be due to the major role of the CYP3A4 and CYP3A5 enzymes in the second step of clopidogrel bioactivation which may substantiate the effect of their genetic polymorphisms on clopidogrel exposure.…”

Section: Genetic Factors Contributing To Clopidogrel Htprmentioning

confidence: 99%

The Personalization of Clopidogrel Antiplatelet Therapy: The Role of Integrative Pharmacogenetics and Pharmacometabolomics

Amin

Chin

Noor

et al. 2017

Cardiology Research and Practice

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Dual antiplatelet therapy of aspirin and clopidogrel is pivotal for patients undergoing percutaneous coronary intervention. However, the variable platelets reactivity response to clopidogrel may lead to outcome failure and recurrence of cardiovascular events. Although many genetic and nongenetic factors are known, great portion of clopidogrel variable platelets reactivity remain unexplained which challenges the personalization of clopidogrel therapy. Current methods for clopidogrel personalization include CYP2C19 genotyping, pharmacokinetics, and platelets function testing. However, these methods lack precise prediction of clopidogrel outcome, often leading to insufficient prediction. Pharmacometabolomics which is an approach to identify novel biomarkers of drug response or toxicity in biofluids has been investigated to predict drug response. The advantage of pharmacometabolomics is that it does not only predict the response but also provide extensive information on the metabolic pathways implicated with the response. Integrating pharmacogenetics with pharmacometabolomics can give insight on unknown genetic and nongenetic factors associated with the response. This review aimed to review the literature on factors associated with the variable platelets reactivity response to clopidogrel, as well as appraising current methods for the personalization of clopidogrel therapy. We also aimed to review the literature on using pharmacometabolomics approach to predict drug response, as well as discussing the plausibility of using it to predict clopidogrel outcome.

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“…However, despite dual antiplatelet therapy, a large number of patients present incomplete platelet inhibition (2, 3), and a high residual platelet reactivity on clopidogrel, also termed poor response to clopidogrel (PRC), is associated with increased cardiovascular ischemic events and an unfavorable prognosis (4). Mechanisms contributing to PRC are not entirely well known and are probably multifactorial (5–7).…”

Section: Introductionmentioning

confidence: 99%

Genotyping of six clopidogrel-metabolizing enzyme polymorphisms has a minor role in the assessment of platelet reactivity in patients with acute coronary syndrome

Lagunar

Sánchez²,

Conesa‐Zamora³

et al. 2017

Anatol J Cardiol

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Objective:To evaluate the contribution of six polymorphisms to the platelet reactivity in patients with acute coronary syndrome (ACS) treated with clopidogrel.Methods:Cross-sectional study of 278 consecutive patients with ACS. Detailed clinical information for each patient was collected and genotypes (CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*17, CYP3A4*1B, and PON1-Q192R) were evaluated with TaqMan® and KASPar® assays. Platelet reactivity was measured with VerifyNow®.Results:Mean age of patients was 66±11 years and 182 (65.5%) patients presented ACS without ST-segment elevation. A total of 206 (74.1%) patients presented poor response to clopidogrel (PRC). CYP2C19*2 polymorphism (p=0.038) was associated with PRC in the univariate setting. In the multiple logistic regression analysis, the risk factors for PRC were the presence of CYP3A4*1B allele (odds ratio [OR] 4.03; 95% confidence interval [CI] 1.01–16.34), age (OR 1.43; 95% CI 1.03–2.00), and body mass index (OR 4.05; 95% CI 1.21–13.43), whereas elevated hemoglobin was a protective factor. Discrimination of PRC through the model that included the six polymorphisms added modest information to the model based on clinical variables (C statistic difference 3.9%).Conclusion:CYP3A4*1B allele may be an independent determinant of PRC in patients with ACS, although the variability in response to clopidogrel explained by the six polymorphisms is poor when compared to clinical variables. (Anatol J Cardiol 2017; 17: 303-12)

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Genetic determinants of clopidogrel responsiveness in Koreans treated with drug-eluting stents

Cited by 29 publications

References 40 publications

Genotype Frequencies of CYP2C19, P2Y<sub>12</sub> and GPIIIa Polymorphisms in Coronary Heart Disease Patients of Han Ethnicity, and Their Impact on Clopidogrel Responsiveness

Genotype Frequencies of CYP2C19, P2Y<sub>12</sub> and GPIIIa Polymorphisms in Coronary Heart Disease Patients of Han Ethnicity, and Their Impact on Clopidogrel Responsiveness

The Personalization of Clopidogrel Antiplatelet Therapy: The Role of Integrative Pharmacogenetics and Pharmacometabolomics

Genotyping of six clopidogrel-metabolizing enzyme polymorphisms has a minor role in the assessment of platelet reactivity in patients with acute coronary syndrome

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