中国人群中CYP2C19基因多态性对质子泵抑制药治疗消化性溃疡疗效影响的Meta分析

Meta-analysis of the Influence of CYP2C19 Genetic Polymorphisms on the Efficacy of Proton Pump Inhibitors in the Treatment of Peptic Ulcer in Chinese Subjects

目的:采用Meta分析方法评价中国人群中药物代谢酶CYP2C19基因多态性与质子泵抑制药对消化性溃疡愈合率的关系,以期为临床用药与基因检测提供循证依据。方法:检索Sino Med、中国知网、维普期刊数据库、万方数据库、PubMed、Embase中有关CYP2C19基因多态性与质子泵抑制药治疗消化性溃疡的临床研究文献。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与Stata 13.0软件进行Meta分析。结果:共纳入8篇文献,包含1 197例对象。Meta分析结果显示:不考虑质子泵抑制药类型,CYP2C19强代谢型(EM)的消化性溃疡愈合率低于与中间代谢型(IM)(OR=0.63,95%CI:0.46~0.86,P<0.05),EM型的消化性溃疡愈合率低于与弱代谢型(PM)(OR=0.45,95%CI:0.29~0.69,P<0.05),但IM型与PM型消化性溃疡愈合率的差异无统计学意义(OR=0.68,95%CI:0.44~1.04,P>0.05)。亚组分析仅发现同样结果存在于奥美拉唑中,EM型消化性溃疡愈合率低于IM型低(OR=0.59,95%CI:0.36~0.97,P<0.05),EM型消化性溃疡愈合率亦低于PM型(OR=0.29,95%CI:0.13~0.62,P<0.05),但IM型与PM型的差异无统计学意义(P>0.05)。其他质子泵抑制药如雷贝拉唑、埃索美拉唑、艾普拉唑等未发现上述差异。结论:中国人群中CYP2C19基因多态性影响奥美拉唑的消化性溃疡愈合率疗效,但不影响埃索美拉唑、雷贝拉唑、艾普拉唑等其他质子泵抑制药的疗效。因此,在应用奥美拉唑治疗消化性溃疡时,有必要对患者的CYP2C19进行基因检测,以指导个体化给药方案的制订。

Objective： To systematically review the influence of CYP2C19 genetic polymorphisms on the efficacy of proton pump inhibitors in the treatment of peptic ulcer in Chinese subjects. Methods： Such databases as SinoMed, CNKI, WanFang data, CQVIP, PubMed and Embase were electronically searched for the clinical studies on CYP2C19 genetic polymorphisms, proton pump inhibitors and peptic ulcer. According to the inclusion and exclusion criteria, the literatures were screened out, the data were extracted, and the methodological quality of the included studies was also examined. Meta-analysis was then performed using RevMan 5.3 and Stata 13.0 software. Results： A total of 8 studies involving 1 197 Chinese subjects were included. The results of meta-analysis showed that CYP2C19 genetic polymorphism of patients was significantly associated with the healing rate of peptic ulcer treated with proton pump in- hibitors. No thinking about the type of proton pump inhibitors, the peptic ulcer healing rate for extensive metabolizer （EM） phenotype was remarkably lower than that for intermediate metabolizer （IM） phenotype （ OR = 0.63, 95% CI： 0. 46-0.86, P 〈 0.05 ） or poor metabolizer （PM） phenotype （ OR = 0.45, 95% CI： 0. 29-0.69, P 〈 0.05 ）, respectively. However, the similar trends were not showed in IM phenotype and PM phenotype （ OR =0.68, 95% CI： 0. 44-1.04, P 〉0.05）. Subgroup analysis further showed that only in omeprazole treatment, the peptic ulcer healing rate for EM phenotype was remarkably lower than that for IM phenotype （ OR = 0.59, 95% CI： 0. 36-0.97, P 〈 0.05）, or PM phenotype （ OR = 0.29, 95% CI： 0. 13-0.62, P 〈 0.05）, respectively. However, no difference was found between IM and PM phenotype. The simitar trends were not showed in the other proton pump inhibitors, including rabeprazole, esomeprazole and ilaprazole. Conclusion： CYP2C19 genetic polymorphism only affects the efficacy of omeprazole for the therapy of peptic ulcer, while shows no influence on the efficacy of the other proton pump inhibitors in Chinese subjects. Therefore, patients with peptic ulcer should receive genetic testing of CYP2C19 polymorphisms before the use of omeprazole.