Abstract
INTRODUCTION: Carboxylesterase 1 (CES1) is the primary enzyme responsible for converting clopidogrel into biologically inactive carboxylic acid metabolites. METHODS: We genotyped a functional variant in CES1, G143E, in participants of the Pharmacogenomics of Anti-Platelet Intervention (PAPI) study (n=566) and in 350 patients with coronary heart disease treated with clopidogrel, and carried out an association analysis of bioactive metabolite levels, on-clopidogrel ADP-stimulated platelet aggregation, and cardiovascular outcomes. RESULTS: The levels of clopidogrel active metabolite were significantly greater in CES1 143E-allele carriers (P=0.001). Consistent with these findings, individuals who carried the CES1 143E-allele showed a better clopidogrel response as measured by ADP-stimulated platelet aggregation in both participants of the PAPI study (P=0.003) and clopidogrel-treated coronary heart disease patients (P=0.03). No association was found between this single nucleotide polymorphism and baseline measures of platelet aggregation in either cohort. CONCLUSION: Taken together, these findings suggest, for the first time, that genetic variation in CES1 may be an important determinant of the efficacy of clopidogrel.
Original language | English (US) |
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Pages (from-to) | 1-8 |
Number of pages | 8 |
Journal | Pharmacogenetics and Genomics |
Volume | 23 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2013 |
Externally published | Yes |
Keywords
- CES1
- carboxylesterase 1
- clopidogrel
- percutaneous coronary intervention
- pharmacogenetics
ASJC Scopus subject areas
- Genetics(clinical)
- Genetics
- Molecular Medicine
- Molecular Biology
- Pharmacology, Toxicology and Pharmaceutics(all)