奥美拉唑对氯吡格雷抗血小板作用的影响及CYP2C19基因多态性的作用

Impact of proton pump inhibitor omeprazole on the antiplatelet effect of clopidogrel in individuals with various CYP2C19 ＊ 2 genotypes

目的探讨质子泵抑制剂奥美拉唑对于氯吡格雷抗血小板聚集作用的影响，并研究CYP2C19的基因多态性与氯吡格雷抗血小板聚集作用的关系。方法将414例诊断为急性冠脉综合征且进行介入治疗的患者给予阿司匹林和氯吡格雷双联抗血小板治疗，术前及术前7天分别测定血小板聚集率（plateletaggregation，PA）后分别联用奥美拉唑（224例）和西咪替丁（190例）治疗，14天后再测定PA；应用聚合酶链反应一限制性片段长度多态性和DNA测序的方法对CYP2C19＊2（681G／A）进行基因分型，分析基因多态性对氯吡格雷抗血小板作用的影响。结果奥美拉唑组和西咪替丁组患者术前的PA比较差异无统计学意义，在术后7天和术后21天两组相同基因型患者PA比较差异无统计学意义，但术后7天、21天两组CYP2C19＊2GG型和GA型患者的PA明显小于AA型患者的PA，奥美拉唑组GG、GA、AA基因型术后7天的PA分别为（37．1±9．2）％、（37．4±9．4）％vs（45．6±8．9）％，术后21天的PA为（22．0±8．O）％、（22．6±7．2）％、（36．9士9．2）％，西眯替丁组GG、GA、AA基因型患者术后7天的PA为（38．4±8．3）％、（37．1±7．3）％、（48．5±7．2）％，术后21天的PA为（24．6±7．4）％、（22．9±7．7）％、（36．8±8．9）％（P〈O．05）。结论奥美拉唑不影响氯吡格雷抗血小板效应。CYP2C19＊2的AA基因变异影响氯吡格雷对血小板的抑制效果。

Objective To investigate the impact of omeprazole on platelet response to clopidogrel and the effect of polymorphisms of CYP2C19 on the antiplatelet effect of clopidogrel. Methods Platelet aggregation （PA） was assessed before 300 mg aspirin plus 300 mg loading dose of clopidogrel and after 300 mg aspirin plus 75 mg maintenance dose of clopidogrel 7 days later in 414 patients with acute coronary syndrome who have undergone percutaneous coronary intervention （PCI）. Thereafter, gastric mucosal protective drugs were given （omeprazolem 20 rag, n= 224 or cimetidine 800 mg, n= 190）. Fourteen days later, PA was measured again. Genotypes of CYP2C19 ＊ 2 were analyzed with polymerase chain reaction- restriction fragment length polymorphism （PCR-RFLP）. Results After taken aspirin and clopidogrel, PA has decreased significantly in both groups. Compared with cimetidine, omeprazole had no significant impact on PA on 7 and 21 days post PCI. Compared with homozygotes or heterozygotes for the wild-type CYP2C19 ~ 2, patients with CYP2C19 ＊ 2 AA genotype had significantly higher PA on 7 and 21 days post PCI （P（ 0.05）. Conclusion No attenuating effect on platelet response to clopidogrel has been observed for Omeprazole. The variant of CYP2C19 ＊ 2 AA genotype is significantly associated with attenuated response to clopidogrel.