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Multiple genetic mutations increase the risk of thrombosis associated with clopidogrel after percutaneous coronary

Hui Jin1, Jinfei Song1, Xiaoying Shen1

  • 1Department of Pharmacy, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, 200240, China.

Pharmacogenomics
|March 9, 2023
PubMed

Insights

Multiple genetic mutations in CYP2C19, PON1, and ABCB1 genes significantly impact dual antiplatelet therapy effectiveness post-PCI. The number of dysfunctional genes correlates with recurrent thrombosis risk, not bleeding.

Area of Science:

  • Pharmacogenomics
  • Cardiovascular Medicine
  • Genetics

Background:

  • Dual antiplatelet therapy (DAPT) is standard after percutaneous coronary intervention (PCI).
  • The impact of combined genetic variations in CYP2C19, PON1, and ABCB1 on DAPT outcomes is not well understood.
  • Understanding these genetic influences is crucial for optimizing patient treatment.

Purpose of the Study:

  • To investigate the effect of multiple gene mutations on clopidogrel response and clinical outcomes.
  • To determine the relationship between genetic polymorphisms and thrombotic or bleeding events.
  • To evaluate the predictive value of combined gene analysis for clinical outcomes after PCI.

Main Methods:

  • Genotyping of CYP2C19, PON1, and ABCB1 genes in 263 Chinese Han patients.
  • Assessment of platelet aggregation rates and thrombosis risk.
  • Comparison of clopidogrel response and clinical outcomes based on the number of genetic mutations.

Main Results:

  • 74% of patients harbored more than two genetic mutations.
  • Genetic mutations were associated with higher platelet aggregation rates and increased risk of thrombotic events.
  • No significant association was found between genetic mutations and bleeding events.
  • The number of dysfunctional genes directly correlated with recurrent thrombosis risk.

Conclusions:

  • Considering polymorphisms in CYP2C19, PON1, and ABCB1 collectively offers superior prediction of clinical outcomes compared to individual gene analysis or platelet aggregation rates.
  • This multi-gene approach may aid in personalized DAPT strategies post-PCI.

Keywords:
bleedingdual antiplatelet therapygenetic polymorphismplatelet aggregation ratethrombosis

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