CYP2C19基因多态性与氯吡格雷疗效的相关性研究

目的 探讨CYP2C19*2、CYP2C19*3基因多态性与非心源性栓塞所致缺血性卒中患者应用氯吡格雷临床疗效的关系.方法 前瞻性连续纳入非心源性栓塞急性缺血性脑血管病患者102例,确定患者与氯吡格雷代谢相关的CYP2C 19基因型,分为快代谢型、中间代谢型及慢代谢型.患者连续服用氯吡格雷75 mg/d,至少7d后,用血栓弹力图仪测定氯吡格雷对血小板的抑制率.并对其进行至少1年的临床随访,记录患者的临床终点事件,比较不同基因型患者的氯吡格雷疗效和临床预后.结果 快代谢型、中间代谢型和慢代谢型3型患者血小板抑制率分别为(41.59±18.17)％、(38.33±28.92)％及(21.17±15.66)％,差异无统计学意义(P=0.163);3型患者氯吡格雷不敏感发生率分别为29.4％、42.9％和64.3％,差异无统计学意义(P=0.069).缺血性卒中发生后1年内,14例患者发生临床事件,其中快代谢型患者8例,中间代谢型6例.不同基因型患者间发生临床事件的比例差异无统计学意义(P＞0.05).结论 对于非心源性的急性缺血性卒中患者,服用氯吡格雷后,CYP2C19基因型尚不能预测氯吡格雷疗效及临床预后.

Effects of cytochrome P450 2C19 polymorphisms on the efficacy of clopidogrel

Objective To investigate the effect of CYP2C19 polymorphisms on the efficacy of clopidogrel and clinical outcomes among recent non-cardioembolic ischemic stroke patients.Methods A total of 102 non-cardioembolic ischemic stroke patients treated with clopidogrel were enrolled into the study,who were categorized as extensive metabolizers,intermediate metabolizers and chronic metabolizers based on CYP2C19 genotype.The platelet inhibitive rate with clopidogrel therapy for at least 7 days was measured using thrombelastography.All the patients were followed up for at least 1 year,and the occurrence of secondary ischemic stroke,myocardial infarction,all-cause of death as well as bleeding events were recorded.Results The platelet inhibitive rates of extensive metabolic type,intermediate metabolic type and chronic metabolic type were (41.59±18.17)％,(38.33±28.92)％ and (21.17±15.66)％,respectively,there was no significant difference(P=0.163).The occurrence rates of clopidogrel resistance in the three groups were 29.4％,42.9％ and 64.3％,there was no significant difference (P=0.069).There was no significant difference in clinical events among different gene types patients.Conclusion For non-cardioembolic ischemic stroke patients,the efficacy of clopidogrel and clinical outcomes cannot be predicted only based on CYP2C19 polymorphisms.