The impact of CYP2C19*2, CYP4F2*3, and clinical factors on platelet aggregation, CYP4F2 enzyme activity, and 20-hydroxyeicosatetraenoic acid concentration in patients treated with dual antiplatelet therapy

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Abstract

The aim of the current study was to evaluate the impact of CYP2C19*2 (rs4244285), CYP4F2*3 (rs2108622), and nongenetic factors on platelet aggregation and to investigate the mechanism of CYP4F2's effect on platelet aggregation in the patients treated with dual antiplatelet therapy. A total of 146 patients were included in this study. Ticagrelor or clopidogrel were administered in a loading dose of 180 mg and 600 mg, respectively, in combination with aspirin (300 mg). Blood samples for analysis were taken the next morning after antiplatelet therapy induction. Clopidogrel users with the CYP2C19*1*2 variant had higher platelet aggregation values (median 43, range 30–54%Agr) compared with *1*1 wild-type carriers (median 33, range 15–77%Agr; P = 0.009). Carriers of the CYP4F2*1*3 variant had higher platelet aggregation values than carriers of the *3*3 variant (median 34, range 8–70%Agr vs. median 24.5, range 10–47%Agr, P = 0.016, respectively). Higher CYP4F2 concentrations were detected in clopidogrel users than in ticagrelor users (median 3.6, range 1.6–22.0 ng/ml vs. median 2.3, range 1.6–27.2 ng/ml, P = 0.056, respectively) and in carriers of the CYP4F2*1*3 variant compared with carriers of the *1*1 variant (median 4.3, range 1.6–27.2 ng/ml vs. median 2.4, range 1.6–22.0 ng/ml, P = 0.009, respectively). No correlation between plasma 20-hydroxyeicosatetraenoic acid and CYP4F2 enzyme concentrations were detected (r = −0.045, P = 0.587). Our results proved that CYP2C19*2 might significantly affect antiplatelet function of clopidogrel. Plasma CYP4F2 concentrations were significantly lower in ticagrelor users than in clopidogrel users.

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