| Objective: To assess the genotypes and response to clopidogrel and association between genotypes and the risk of clopidogrel resistance by thrombelastography in patients with acute coronary syndrome.Methods: The data from 459 patients with acute coronary symdrome(ACS) received aspirin and clopidogrel were assessed from July 13, 2013 to November 11, 2015 in this observational case control study. The patients who were <30% platelet inhibition were assigned to clopidogrel resistance group, and the patients who were ≥30% platelet inhibition were assigned to normal responsiveness group. The genotype distribution between the groups was assessed, and the relationship between the risk of clopidogrel resistance and genotypes including CYP2C19*2, CYP2C19*3, CYP2C19*17, ABCB1 and PON1.Results: 275 cases were clopidogrel resistance group and 184 cases were normal responsiveness group by the result of TEG. Compared to CYP2C19*1/*1 wild type carriers, CYP2C19*2 and *3 carriers showed a significantly associated with lower platelet inhibition(P=0.048). The platelet inhibition in carriers of at least one CYP2C19 loss-of-function allele was obviously lower than non-carriers(P=0.031). The platelet inhibition in PON1 192 R carriers was lower than in PON1 192 Q carriers(P=0.044). Patients with the CYP2C19*2 and *3 alleles had a greater risk of HPR than CYP2C19 wild type carriers(adjusted P=0.018 and adjusted P=0.005). At least one PON1 192 R carriers predicted significantly higher risk of clopidogrel resistance than PON1 192 Q carriers(adjusted P=0.021). Individual CYP2C19*17 and ABCB1 variants did not differ significantly between the two groups.Conclusion: In conclusion, CYP2C19 and PON1 Q192 R genotypes influence ADP-induced platelet inhibition by TEG in ACS patients treated clopidogrel. In addition, loss-of-function CYP2C19 alleles, PON1 192 R genotypes are independent risk factors of HPR, which is measured by the relative platelet inhibition. |
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