| Clopidogrel is a commonly used drug in clinical antiplatelet therapy, and widely used in acute coronary syndromes and percutaneous coronary intervention with aspirin after stent implantation worldwide as the standards program of antiplatelet therapy. However, considerable patients who received conventional doses of clopidogrel, occurred the thrombotic events, the phenomenon is defined as clopidogrel resistance (CR). Clopidogrel is a prodrug that has to be converted to an active metabolite by hepatic cytochrome P450 (CYP) isoenzymes to inhibit platelet aggregation. Individual variability of platelet inhibition by clopidogrel suggests a possibility for genetic factors having a significant influence on clopidogrel responsiveness. In this study, we want to clarify the relationship between CYP2C19 gene polymorphism and CR by PCR-RFLP and pyrosequencing analysis.Methods: A total of 1102 cases of coronary heart disease were involved to receive clopidogrel(600mg or 300mg) plus aspirin(300mg), and their platelet aggregation were detected by optical turbidimetry (20 mol/L of ADP-induced). CR is defined as platelet aggregation rate (PAR)≥70%; and PAR <70% is considered as non-clopidogrel resistance (NCR). All cases were detected to identify cytochrome P450 2C19 gene tag single nucleotide polymorphism (tagSNPs) genotype and allele distribution,by PCR-RFLP and pyrosequencing.Results: (1) The incidence of CR is 15.88%. (2) Cytochrome P450 2C19 rs4244285 locus (681G>A) polymorphism were GG, GA and AA genotypes in CR group and NCR group were 28.6%, 44.5% 26.9% and 46.1%, 45.3%, 8.6%. The incidence of CR is significantly higher in A allele carriers than G allele carriers (OR = 2.123,95% CI: 1.684 ~ 2.675, P <0.001). (3) CYP2C19 gene rs7916649, rs3758581, rs11528090, rs4304697, rs3814637, rs10786172, rs4986893 and rs12248560 polymorphism were no significant correlation with CR (P > 0.05).Conclusion: CYP2C19 gene locus rs4244285 (681G> A) is an independent risk factor for clopidogrel resistance. |
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