Dataset Information

Genome-wide and candidate gene approaches of clopidogrel efficacy using pharmacodynamic and clinical end points-Rationale and design of the International Clopidogrel Pharmacogenomics Consortium (ICPC).

ABSTRACT:

Rationale

The P2Y₁₂ receptor inhibitor clopidogrel is widely used in patients with acute coronary syndrome, percutaneous coronary intervention, or ischemic stroke. Platelet inhibition by clopidogrel shows wide interpatient variability, and high on-treatment platelet reactivity is a risk factor for atherothrombotic events, particularly in high-risk populations. CYP2C19 polymorphism plays an important role in this variability, but heritability estimates suggest that additional genetic variants remain unidentified. The aim of the International Clopidogrel Pharmacogenomics Consortium (ICPC) is to identify genetic determinants of clopidogrel pharmacodynamics and clinical response.

Study design

Based on the data published on www.clinicaltrials.gov, clopidogrel intervention studies containing genetic and platelet function data were identified for participation. Lead investigators were invited to share DNA samples, platelet function test results, patient characteristics, and cardiovascular outcomes to perform candidate gene and genome-wide studies.

Results

In total, 17 study sites from 13 countries participate in the ICPC, contributing individual patient data from 8,829 patients. Available adenosine diphosphate-stimulated platelet function tests included vasodilator-stimulated phosphoprotein assay, light transmittance aggregometry, and the VerifyNow P2Y₁₂ assay. A proof-of-principle analysis based on genotype data provided by each group showed a strong and consistent association between CYP2C19*2 and platelet reactivity (P value=5.1 × 10^-40).

Conclusion

The ICPC aims to identify new loci influencing clopidogrel efficacy by using state-of-the-art genetic approaches in a large cohort of clopidogrel-treated patients to better understand the genetic basis of on-treatment response variability.

SUBMITTER: Bergmeijer TO

PROVIDER: S-EPMC5903579 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Publications

Genome-wide and candidate gene approaches of clopidogrel efficacy using pharmacodynamic and clinical end points-Rationale and design of the International Clopidogrel Pharmacogenomics Consortium (ICPC).

Bergmeijer Thomas O TO Reny Jean-Luc JL Pakyz Ruth E RE Gong Li L Lewis Joshua P JP Kim Eun-Young EY Aradi Daniel D Fernandez-Cadenas Israel I Horenstein Richard B RB Lee Ming Ta Michael MTM Whaley Ryan M RM Montaner Joan J Gensini Gian Franco GF Cleator John H JH Chang Kiyuk K Holmvang Lene L Hochholzer Willibald W Roden Dan M DM Winter Stefan S Altman Russ B RB Alexopoulos Dimitrios D Kim Ho-Sook HS Déry Jean-Pierre JP Gawaz Meinrad M Bliden Kevin K Valgimigli Marco M Marcucci Rossella R Campo Gianluca G Schaeffeler Elke E Dridi Nadia P NP Wen Ming-Shien MS Shin Jae Gook JG Simon Tabassome T Fontana Pierre P Giusti Betti B Geisler Tobias T Kubo Michiaki M Trenk Dietmar D Siller-Matula Jolanta M JM Ten Berg Jurriën M JM Gurbel Paul A PA Hulot Jean-Sebastien JS Mitchell Braxton D BD Schwab Matthias M Ritchie Marylyn DeRiggi MD Klein Teri E TE Shuldiner Alan R AR

American heart journal 20171217

<h4>Rationale</h4>The P2Y<sub>12</sub> receptor inhibitor clopidogrel is widely used in patients with acute coronary syndrome, percutaneous coronary intervention, or ischemic stroke. Platelet inhibition by clopidogrel shows wide interpatient variability, and high on-treatment platelet reactivity is a risk factor for atherothrombotic events, particularly in high-risk populations. CYP2C19 polymorphism plays an important role in this variability, but heritability estimates suggest that additional g ...[more]

PMID: 29653637

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Dataset Information

Genome-wide and candidate gene approaches of clopidogrel efficacy using pharmacodynamic and clinical end points-Rationale and design of the International Clopidogrel Pharmacogenomics Consortium (ICPC).

Rationale

Study design

Results

Conclusion

Publications

Genome-wide and candidate gene approaches of clopidogrel efficacy using pharmacodynamic and clinical end points-Rationale and design of the International Clopidogrel Pharmacogenomics Consortium (ICPC).

Similar Datasets

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