Genetic polymorphisms of
cytochrome P450 (CYP)
isoforms may promote variability in platelet response to
clopidogrel. This study was conducted to analyze, in 603 patients with non-ST elevation
acute coronary syndromes, the effect of
CYP3A4,
CYP3A5, and
CYP2C19 gene polymorphisms on
clopidogrel response and post-treatment platelet reactivity assessed by
adenosine diphosphate (
ADP)-induced platelet aggregation,
vasodilator-stimulated phosphoprotein phosphorylation index, and
ADP-induced
P-selectin expression. The
CYP2C19*2 polymorphism was significantly associated with
ADP-induced platelet aggregation,
vasodilator-stimulated phosphoprotein phosphorylation index, and
ADP-induced
P-selectin expression in recessive (p <0.01, p <0.007, and p <0.06, respectively) and codominant (p <0.08, p <0.0001, and p <0.009, respectively) models, but the
CYP3A4*1B and
CYP3A5*3 polymorphisms were not. The
CYP2C19*2 allele carriers exhibited the highest platelet index levels in multivariate analysis (p = 0.03). After covariate adjustment, the
CYP2C19*2 allele was more frequent in
clopidogrel nonresponders, defined by persistent high post-treatment platelet reactivity (
ADP-induced platelet aggregation >70%; p = 0.03). In conclusion, the present data suggest that the CYPC19*2 allele influences post-treatment platelet reactivity and
clopidogrel response in patients with non-ST elevation
acute coronary syndromes.