What question did this study set out to answer?

To assess the effects of the CES1A2 A(-816)C polymorphism, other genetic variants, and clinical factors on clopidogrel response variability and stent thrombosis risk.

February 17, 2014Pharmacogenetics and Genomics

The effects of CES1A2 A(−816)C and CYP2C19 loss-of-function polymorphisms on clopidogrel response variability among Chinese patients with coronary heart disease

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Why the study?

Do CES1A2 A(-816)C and CYP2C19 loss-of-function polymorphisms affect clopidogrel response variability and the risk of stent thrombosis in Chinese patients with coronary heart disease?

Population

162 Chinese patients with coronary heart disease treated with aspirin and clopidogrel, along with a…

Comparison

Presence of CES1A2 AC, CYP2C19 *2/*3, PON1… vs Absence of these polymorphisms

Design

Cohort

Authors

CXCheng XieShenyang Institute of Automation XDXiaoliang DingSoochow University JGJie GaoFujian Medical University

Discussion

Member takes

Implication

CYP2C19 LOF alleles may aid stent thrombosis risk stratification in Chinese patients on clopidogrel; leaves open CES1A2 role and requires prospective validation.

Key Points

To assess the effects of the CES1A2 A(-816)C polymorphism, other genetic variants, and clinical factors on clopidogrel response variability and stent thrombosis risk.
Genotyped 162 coronary heart disease patients receiving aspirin and clopidogrel for CES1A2 A(-816)C, CYP2C19 *2/*3, PON1 Q192R, and ABCB1 C3435T, assessing platelet reactivity via VASP-PRI.
Conducted a case-control study matching 22 stent-implanted patients who developed stent thrombosis with 86 thrombosis-free controls.
Platelet reactivity (VASP-PRI) values were significantly higher in carriers of the CES1A2 -816C allele (P=0.014) and CYP2C19 loss-of-function alleles (P=0.004).
CYP2C19 loss-of-function alleles were associated with an increased risk of stent thrombosis (adjusted OR = 4.28, P=0.033), whereas the CES1A2 -816C allele showed no significant association.
CYP2C19 and CES1A2 variants accounted for 6.1% and 3.7% of response variability, respectively, expanding to 12.5% when combined with clinical factors like BMI and triglycerides, while PON1 and ABCB1 had no significant effect.

Structured PICO

Do CES1A2 A(-816)C and CYP2C19 loss-of-function polymorphisms affect clopidogrel response variability and the risk of stent thrombosis in Chinese patients with coronary heart disease?

Population

162 Chinese patients with coronary heart disease treated with aspirin and clopidogrel, along with a case-control cohort of 22 patients with stent thrombosis matched with 86 stent thrombosis-free controls.

Intervention

Presence of CES1A2 A(-816)C, CYP2C19 *2/*3 (loss-of-function), PON1 Q192R, and ABCB1 C3435T polymorphisms

Comparator

Absence of these polymorphisms (wild-type carriers)

Outcome

Platelet reactivity analyzed using the VASP-PRI assay and development of stent thrombosissurrogate

Both CES1A2 -816C and CYP2C19 loss-of-function alleles are associated with attenuated platelet reactivity to clopidogrel, and CYP2C19 LOF predicts stent thrombosis in Chinese patients with coronary heart disease.

Cite This Study

Xie et al. (2014) studied this question.

synapsesocial.com/papers/6a7138908031ec7bb1dcd3eb https://doi.org/10.1097/fpc.0000000000000035

Topics

Dual antiplatelet therapy

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Implication

CYP2C19 LOF alleles may aid stent thrombosis risk stratification in Chinese patients on clopidogrel; leaves open CES1A2 role and requires prospective validation.

The effects of CES1A2 A(−816)C and CYP2C19 loss-of-function polymorphisms on clopidogrel response variability among Chinese patients with coronary heart disease

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Topics

The effects of CES1A2 A(−816)C and CYP2C19 loss-of-function polymorphisms on clopidogrel response variability among Chinese patients with coronary heart disease

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Topics

Also Consider