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CES1A -816C as a genetic marker to predict greater platelet clopidogrel response in patients with percutaneous

Jian-Jun Zou1, Shao-Liang Chen, Hong-Wei Fan

  • 1*Division of Clinical Pharmacology, General Clinical Research Center; †Division of Cardiovascular Medicine, Department of Medicine, Nanjing Heart Center; and ‡Central Laboratory, General Clinical Research Center, Nanjing Medical University Nanjing First Hospital, Nanjing, China; and §Department of Pharmacology, Nanjing Medical University School of Pharmacy, Nanjing, China.

Journal of Cardiovascular Pharmacology
|February 11, 2014
PubMed

Insights

The CES1A -816C variant is linked to a better clopidogrel response in patients undergoing percutaneous coronary intervention. This genetic marker may predict increased platelet aggregation compared to the CES1A -816A variant.

Area of Science:

  • Pharmacogenomics
  • Cardiovascular Medicine
  • Genetics

Background:

  • Clopidogrel is a crucial antiplatelet medication used after percutaneous coronary intervention (PCI).
  • Individual response to clopidogrel can vary, impacting treatment efficacy and safety.
  • Genetic factors, including polymorphisms in CES1A and CYP2C19, are known to influence clopidogrel metabolism and response.

Purpose of the Study:

  • To investigate the association between the CES1A -816A/C polymorphism and clopidogrel response in patients undergoing PCI.
  • To determine if CES1A -816A/C genotype influences platelet aggregation and stent thrombosis risk.

Main Methods:

  • Patients undergoing PCI received clopidogrel loading and maintenance doses.
  • Genotyping was performed for CYP2C19 (*2, *3, *17) and CES1A -816A/C polymorphisms.
  • Adenosine diphosphate-induced maximum platelet aggregation (MPA) was measured, and 1-year stent thrombosis (ST) incidence was assessed.

Main Results:

  • The CES1A -816A/C polymorphism was independently associated with MPA (β = 6.76).
  • In patients without CYP2C19 variants, CES1A -816C carriers showed significantly lower MPA (21.5%) compared to non-carriers (31.7%, P = 0.001).
  • A trend towards lower stent thrombosis was observed in CES1A -816C carriers.

Conclusions:

  • The CES1A -816C variant is associated with a greater platelet response to clopidogrel compared to the CES1A -816A variant.
  • This finding is particularly relevant in patients treated with PCI who do not carry CYP2C19 variants affecting clopidogrel metabolism.
  • CES1A -816A/C genotyping may aid in personalizing clopidogrel therapy to optimize outcomes.

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