Key result
CYP2C19 polymorphism was significantly associated with the plasma concentration ratios of clopidogrel to its inactive metabolite SR26334 across metabolism genotype groups (P<0.001).
Why the study?
Do CYP2C19 loss-of-function variants influence the metabolism of clopidogrel in patients on maintenance therapy?
Observational (n=366)
Do CYP2C19 loss-of-function variants influence the metabolism of clopidogrel in patients on maintenance therapy?
CYP2C19 loss-of-function variants (*2 and *3 alleles) significantly alter clopidogrel metabolism, resulting in lower active drug levels in poor metabolizers.
Supports CYP2C19 effect on clopidogrel metabolism in maintenance patients; leaves open whether genotyping improves clinical outcomes.
WHAT IS KNOWN AND OBJECTIVE: Variation of the cytochrome P450 2C19 gene coding for the CYP2C19 enzyme has been reported to be associated with clopidogrel response variability. The activity of the CYP2C19 enzyme is genetically influenced by polymorphisms of its gene. METHODS: This study was conducted to assess the impact of CYP2C19 polymorphism on the clopidogrel metabolism, indirectly selecting the plasma concentration ratios of clopidogrel to its inactive metabolite SR26334 as an evaluation index. Genotyping and plasma concentration results of 366 patients on clopidogrel maintenance therapy (75 mg daily dose) were analysed in this study. CYP2C19 genotypes were determined by PCR-restriction fragment length polymorphism method. RESULTS AND DISCUSSION: As for CYP2C19, patients were classified into three metabolism genotype groups: EM (44·3%), IM (43·4%) and PM (12·3%). The mean plasma concentration ratio of clopidogrel to its inactive metabolite SR26334 for the entire sample was 0·507. The plasma concentration ratios of the 3 metabolism groups were significantly different (P < 0·001). The lowest plasma concentration ratio value was observed for PM patients. WHAT IS NEW AND CONCLUSION: Polymorphism of CYP2C19 was significantly associated with plasma concentration ratios of clopidogrel to its inactive metabolite SR26334. Clopidogrel metabolism was regulated by CYP2C19. The *2 and *3 allele carriage were independently associated with the antiplatelet effect of chronic clopidogrel therapy.
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Lin et al. (2015) conducted an observational in Patients on clopidogrel maintenance therapy (n=366). CYP2C19 polymorphism vs. Different CYP2C19 metabolism genotype groups was evaluated on Plasma concentration ratios of clopidogrel to its inactive metabolite SR26334 (p=<0.001). CYP2C19 polymorphism was significantly associated with the plasma concentration ratios of clopidogrel to its inactive metabolite SR26334 across metabolism genotype groups (P<0.001).
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