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CYP2C19基因多态性对质子泵抑制剂、阿莫西林和左氧氟沙星三联疗法根除幽门螺杆菌的影响。

Effect of CYP2C19 Gene Polymorphisms on Proton Pump Inhibitor, Amoxicillin, and Levofloxacin Triple Therapy for Eradication of Helicobacter Pylori.

作者信息

Lin Yun-An, Wang Hong, Gu Zhu-Jun, Wang Wen-Jia, Zeng Xiao-Yan, Du Yan-Lei, Ying Song-Song, Zhang Bo-Hua

机构信息

Department of Gastroenterology, Guangzhou First People's Hospital, Guangzhou, Guangdong, China (mainland).

出版信息

Med Sci Monit. 2017 Jun 3;23:2701-2707. doi: 10.12659/msm.901514.

Abstract

BACKGROUND The effects of PPI are variable owing to the CYP2C19 polymorphisms. However, whether the polymorphisms could affect the Hp eradication efficacy of triple therapy is still not clear. The present study aimed to assess the effects of CYP2C19 gene polymorphisms on proton pump inhibitor (PPI), amoxicillin, and levofloxacin triple therapy for Helicobacter pylori (Hp) eradication. MATERIAL AND METHODS We randomly assigned 160 Hp-positive patients with chronic gastritis to 2 groups to receive either 20 mg bid omeprazole (OAL group, n=80) or 10 mg bid rabeprazole (RAL group, n=80), combined with 1000 mg bid amoxicillin and 500 mg qd levofloxacin. The 2 groups were treated for 10 days. The CYP2C19 genotypes included wild-type, M1 mutant gene (*2, the mutation of exon 5), and M2 mutant gene (*3, the mutation of exon 4) identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFIP). According to CYP2C19 genotype combinations, the patients were divided into extensive metabolizer (EM), intermediate metabolizer (IM), and poor metabolizer (PM) subgroups. The eradication efficacy of Hp was evaluated by 14C-UBT at 28 days after treatment. RESULTS The trial was completed by 155 patients. Hp eradication rates in OAL and RAL groups were 78.2% and 88.3%, respectively, on per-protocol (PP) analysis, indicating no significant difference (P>0.05). Regarding CYP2C19 genotypes, eradication rates of 60.7%, 84.2%, and 100% were obtained for EM, IM, and PM subgroups, respectively, of the OAL group. EM group eradication rates were significantly lower than IM and PM group values (P<0.05). In the RAL group, no such difference was observed (P>0.05). Hp eradication rates were significantly lower in the EM subgroup of the OAL group compared with that of the RAL group. CONCLUSIONS Hp eradication rates were higher in the RAL group than in OAL-treated patients. Interestingly, omeprazole-based therapy was significantly affected by the CYP2C19 genotype, unlike the rabeprazole-based therapy.

摘要

背景

由于CYP2C19基因多态性,质子泵抑制剂(PPI)的效果存在差异。然而,这些多态性是否会影响三联疗法根除幽门螺杆菌(Hp)的疗效仍不清楚。本研究旨在评估CYP2C19基因多态性对质子泵抑制剂(PPI)、阿莫西林和左氧氟沙星三联疗法根除幽门螺杆菌(Hp)的影响。

材料与方法

我们将160例Hp阳性的慢性胃炎患者随机分为两组,分别接受每日2次、每次20mg的奥美拉唑(OAL组,n = 80)或每日2次、每次10mg的雷贝拉唑(RAL组,n = 80),联合每日2次、每次1000mg的阿莫西林和每日1次、每次500mg的左氧氟沙星。两组均治疗10天。通过聚合酶链反应-限制性片段长度多态性(PCR-RFIP)鉴定CYP2C19基因的基因型,包括野生型、M1突变基因(*2,第5外显子突变)和M2突变基因(*3,第4外显子突变)。根据CYP2C19基因型组合,将患者分为快代谢型(EM)、中间代谢型(IM)和慢代谢型(PM)亚组。治疗后28天通过14C-尿素呼气试验(14C-UBT)评估Hp的根除疗效。

结果

155例患者完成了试验。按符合方案(PP)分析,OAL组和RAL组的Hp根除率分别为78.2%和88.3%,差异无统计学意义(P>0.05)。就CYP2C19基因型而言,OAL组的EM、IM和PM亚组的根除率分别为60.7%、84.2%和100%。EM组的根除率显著低于IM组和PM组(P<0.05)。在RAL组中,未观察到此类差异(P>0.05)。OAL组的EM亚组的Hp根除率显著低于RAL组。

结论

RAL组的Hp根除率高于接受奥美拉唑治疗的患者。有趣的是,与基于雷贝拉唑的疗法不同,基于奥美拉唑的疗法受CYP2C19基因型的影响显著。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4fd/5467706/96428b00e0ba/medscimonit-23-2701-g001.jpg

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