Evaluation of response to clopidogrel in patients with CYP2C19*2/*3 polymorphisms and its association with miR-19b expression
摘要
Clopidogrel is a widely used antiplatelet drug for treating acute coronary syndrome. Its metabolism primarily involves the CYP2C19 isoenzyme, with CYP2C192 and CYP2C193 alleles associated with reduced metabolic activity. MicroRNAs, particularly miR-19b, have been linked to cardiovascular disease, but their role in clopidogrel metabolism remains unclear.
MethodsA cross-sectional study was conducted on 50 middle-aged patients on clopidogrel therapy. Platelet aggregation was measured using adenosine diphosphate-induced assays, while CYP2C19*2/*3 polymorphisms were analyzed via RFLP-PCR. The expression of miR-19b was assessed using Real Time-PCR. Statistical analyses were performed to evaluate the relationship between genetic variations, platelet aggregation, and miR-19b expression.
ResultsThe study revealed that 68% of the patients had wild-type genotypes, while 26% had CYP2C19*1/3, 4% had CYP2C193/3, and 2% had CYP2C191/2 genotypes. Patients with CYP2C191/3 polymorphisms exhibited significantly higher mean platelet aggregation compared to those with wild-type genotypes, suggesting a reduced response to clopidogrel treatment. Additionally, the expression of miR-19b did not show significant variation across the different genotypes, indicating that miR-19b may not play a substantial role in clopidogrel metabolism.
ConclusionPatients with CYP2C19*1/*3 polymorphisms have a reduced response to clopidogrel, emphasizing the importance of genetic testing to personalize antiplatelet therapy. The lack of association between miR-19b expression and clopidogrel metabolism suggests that miR-19b is not a critical factor in treatment response.