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A Method to Study the C924T Polymorphism of the Thromboxane A2 Receptor Gene
Published on: April 1, 2019
The CYP2C19*17 variant is not independently associated with clopidogrel response
J P Lewis1, S H Stephens, R B Horenstein
1Division of Endocrinology, Diabetes, and Nutrition and Program in Personalized and Genomic Medicine, School of Medicine, University of Maryland, Baltimore, MD, USA.
Journal of Thrombosis and Haemostasis : JTH
|July 2, 2013
Summary
Genetic variants CYP2C19*2 and CYP2C19*17 influence clopidogrel metabolism. The CYP2C19*2 variant significantly impacts active metabolite levels and platelet aggregation, while CYP2C19*17
Area of Science:
- Pharmacogenomics
- Clinical Pharmacology
- Genetics
Background:
- Cytochrome P450 2C19 (CYP2C19) is crucial for clopidogrel activation.
- Genetic variants CYP2C19*2 and CYP2C19*17 affect CYP2C19 activity and expression.
- Understanding the interplay of these variants is key to optimizing clopidogrel therapy.
Purpose of the Study:
- To determine if CYP2C19*2 and CYP2C19*17 variants independently affect clopidogrel response.
- To investigate genetic linkage disequilibrium (LD) between CYP2C19*2 and CYP2C19*17.
- To clarify the specific contribution of each variant to clopidogrel pharmacodynamics.
Main Methods:
- Genotyping of CYP2C19*2 and CYP2C19*17 in 621 participants of the PAPI Study.
- Evaluation of variant effects on clopidogrel prodrug and active metabolite levels.
- Assessment of adenosine 5'-diphosphate (ADP)-stimulated platelet aggregation before and after treatment, considering LD.
Main Results:
- CYP2C19*2 and CYP2C19*17 variants were found to be in linkage disequilibrium.
- CYP2C19*2 strongly correlated with reduced clopidogrel active metabolite levels and increased platelet aggregation.
- CYP2C19*17 showed minimal association with clopidogrel response after accounting for CYP2C19*2.
Conclusions:
- The observed effects of CYP2C19*17 on clopidogrel response are likely due to its linkage disequilibrium with CYP2C19*2.
- CYP2C19*2 is the primary determinant of altered clopidogrel response among these two variants.
- CYP2C19*17 appears to have a negligible independent effect on clopidogrel pharmacodynamics.
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