CYP2C19基因多态性对PCI术后患者氯吡格雷血药浓度、血小板抑制率和安全性的影响

目的 探讨CYP2C19基因多态性对氯吡格雷血药浓度、血小板抑制率和安全性的影响。方法 根据纳入和排除标准，筛选我院使用氯吡格雷的经皮冠状动脉介入治疗(PCI)术后患者，收集氯吡格雷用药后第6天的血样，采用反相高效液相色谱(RP-HPLC)法测定氯吡格雷血药浓度，非扩增免疫杂交技术检测患者CYP2C19基因型，并通过血栓弹力图来评估血小板抑制率。应用SPSS 20.0对数据进行统计分析。结果 共纳入87例患者，男性46例，女性41例；其中34例为快代谢型，38例中代谢型，15例慢代谢型；结果显示，快、中代谢型的药物浓度无显著性差异（P=0.667），而慢代谢型与快、中代谢型药物浓度有显著性差异(P<0.05)；方差分析和卡方检验显示CYP2C19基因多态性对氯吡格雷的血小板抑制率和安全性的影响有显著性差异(P<0.05）。结论 仅根据CYP2C19基因型指导氯吡格雷临床用药并不一定达到较好的治疗效果，可联合CYP2C19基因型检测与血药浓度监测来指导氯吡格雷的临床个体化给药。

Effect of CYP2C19 gene polymorphism on clopidogrel concentration, platelet inhibition rate and safety in patients after PCI

Objective To explore the effect of CYP2C19 gene polymorphism on clopidogrel plasma concentration, rate of platelet inhibition and safety.Methods We screen the patients who took clopidogrel after PCI in our hospital, according to the inclusion and exclusion criteria. Blood samples were collected on the 6th day after clopidogrel administration. Clopidogrel blood concentration was determine by RP-HPLC. The CYP2C19 genotype was detected by non-amplified immune hybridization. The rate of platelet inhibition was evaluated by the thromboelastogram. The results were analyzed by SPSS 20.0 software.Results A total of 87 patients were recruited, including 46 males and 41 females. Among them, 34 cases were fast metabolism. 38 cases were medium metabolism. 15 cases were slow metabolism. The result showed that there was no significant difference in drug concentration between fast and intermediate metabolism(P=0.667). There was a significant difference in drug concentration between slow metabolism and fast metabolism or medium metabolism(P<0.05). Analysis of variance and chi-square test showed that CYP2C19 gene polymorphism has a significant effect on clopidogrel platelet inhibition rate and safety (P<0.05).Conclusion Guiding clopidogrel clinical medication based on CYP2C19 genotype alone does not necessarily achieve better therapeutic effects. CYP2C19 genotype detection and blood concentration monitoring can be combined to guide the clinical individualized administration of clopidogrel