Polymorphism on CYP2C19 Genes, diabetes and smoker status affect the response to Clopidogrel therapy among Asian patients with acute coronary syndrome

Author : D. Rumenta, R. Sukmawan, R. Dharma, F. Henrika
Upload Date : 19-04-2018

Backgound: Clopidogrel has become standard therapy in patients with acute coronary syndrome (ACS)  post percutaneous coronary intervention (PCI). Enzyme CYP2C19 plays important role in clopidogrel metabolism.  The prevalence of has been known higher in Asians than Caucasians.  Whether CYP2C19 gene polymorphism and cardiac risk factors may affect variability on inhibition of platelets by clopidogrel in Asian patients remained to be defined.

Objective: We sought to define whether polymorphisms on CYP2C19 genes and cardiovascular risk factors may affect the incidence of resistance to clopidogrel in Asian patients with ACS.

Methods: Patients post ACS who mostly underwent PCI and already receiving dual antiplatelet therapy of aspirin and clopidogrel 75 mg at least for 4 weeks, were recruited for the study. We measured platelet aggregation by LTA method using 20 μM ADP. Data of demography, clinical, and current therapy on each patient were collected. Clopidogrel resistance was defined as percent platelet aggregation > 59%. Genetic polymorphism analysis to assess the presence of CYP2C19 *2 sand *3 alleles on each patient were performed by using a Real-time PCR.

Results:  There were 100 post ACS patients recruited for study. The clopidogrel resistant were found in 36 patients (36%). Genetic polymorphism studies revealed: 12% of patients with *2 allele, and 39 % of *3 allele carriers. Multivariate analysis revealed the attributing factors to the incidence of clopidogrel resistance included: diabetes (OR 2.3), non-smoking status (OR 2.3), and carrier of CYP2C19 *2 (OR 3,9), and *3 alleles (OR 2.7). Among them the most dominant predictor was the carrier of CYP2C19 *2 allele (OR 3.9, p = 0.03).

Conclusions: Factors that contribute to clopidogrel resistance in Asian patients with ACS, were: diabetes, non-smoking status, and the carrier of CYP2C19 *2 and *3 alleles, with the most dominant predictor was the presence of CYP2C19 *2 allele. These results may give insight in selecting antiplatelet for personalized therapy of patients with acute coronary syndrome. 

KEYWORDS : clopidogrel resistance, platelet aggregation, CYP2C19 gen

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