中国人群中CYP2C19基因多态性对质子泵抑制剂三联疗法根除幽门螺杆菌疗效影响的Meta分析

Meta analysis of influence of CYP2C19 genetic polymorphisms on eradication rates of Helicobacter pylori infection by proton pump inhibitor based triple therapy

目的:系统评价中国人群中药物代谢酶CYP2C19基因多态性与质子泵抑制剂三联疗法根除幽门螺杆菌疗效的关系,为临床治疗提供循证参考。方法:检索PubMed、Embase、CBM、CNKI、WanFang data、CQVIP等数据库,收集CYP2C19基因多态性与质子泵抑制剂三联疗法根除幽门螺杆菌感染的临床文献。根据纳入和排除标准筛选文献、评价和提取数据后,采用RevMan 5.3和Stata 13.1软件进行Meta分析。结果:共纳入12篇文献,包含1 851例对象。Meta分析结果显示:不考虑质子泵抑制剂类型,CYP2C19强代谢型(EM)、中间代谢型(IM)与弱代谢型(PM)的幽门螺杆菌根治率存在统计学差异[EMvs.IM:OR=0.57,95%CI(0.36,0.88),P<0.05;EMvs.PM:OR=0.39,95%CI(0.25,0.59),P<0.05;IMvs.PM:OR=0.54,95%CI(0.35,0.86),P<0.05]。亚组分析表明含奥美拉唑的三联方案中,EM型幽门螺杆菌根治率明显低于IM型[OR=0.21,95%CI(0.11,0.39),P<0.05],同样结果也发生在EM与PM之间[OR=0.12,95%CI(0.04,0.35),P<0.05],但IM型与PM型间无差异。其他质子泵抑制剂如埃索美拉唑、兰索拉唑、雷贝拉唑等未发现上述差异。结论:中国人群中CYP2C19基因多态性可能影响奥美拉唑三联疗法根除幽门螺杆菌的疗效,但不影响埃索美拉唑、兰索拉唑、雷贝拉唑等质子泵抑制剂的根除效果。

OBJECTIVE To systematically review the influence of CYP2C19 genetic polymorphisms on eradication rates of Helicobacter pylori infection by proton pump inhibitor based triple therapy in Chinese subjects.METHODS Databases, including PubMed, Embase, Cochrane library, CBM, CNKI, WanFang data and CQVIP, were electronically searched for clinical studies on the CYP2C19 genetic polymorphisms, proton pump inhibitors and Helicobacter pylori. According to the inclusion and exclusion criteria, literatures were screened, data were extracted, and the methodologically quality of included studies were also examined. Meta analysis was then performed using RevMan 5.3 and Stata 13.1 softwares.RESULTS A total of 12 studies involving 1851 Chinese subjects were included. The results of Meta analysis showed that CYP2C19 genetic polymorphisms of patients were significantly associated with successful eradication of Helicobacter pylori in the regimen of proton pump inhibitor based triple therapy. Irrespective of specific proton pump inhibitors, eradication rates for Helicobacter pylori in EM phenotype were remarkably lower than in IM phenotype （OR=0.57, 95%CI （0.36, 0.88）, P〈0.05） or PM phenotype （OR=0.39, 95%CI （0.25, 0.59）, P〈0.05）, respectively. Similarly, eradication rates for Helicobacter pylori in IM phenotype were remarkably lower than in PM phenotype （OR=0.54, 95%CI（0.35, 0.86）, P〈0.05）. Subgroup analysis further showed that only in omeprazole based triple therapy, eradication rates for Helicobacter pylori in EM phenotype were remarkably lower than in IM phenotype （OR=0.21, 95%CI （0.11, 0.39）, P〈0.05） or PM phenotype （OR=0.12, 95%CI （0.04, 0.35）, P〈0.05）, respectively. Similar trends were not found in other proton pump inhibitor based triple therapies, including esomeprazole, rabeprazole and lansoprazole.CONCLUSION CYP2C19 genetic polymorphism probably affects the efficacy of omeprazole based triple therapy on the eradication rates of Helicobacter pylori infection, but does not affect the efficacy of other proton pump inhibitor based triple therapies in Chinese subjects.