CYP2C19基因多态性对雷贝拉唑三联疗法根除幽门螺杆菌疗效的影响

目的 分析CYP2C19基因多态性在含雷贝拉唑的不同三联方案中对幽门螺杆菌(Hp)根除率的影响。方法 连续收集128例Hp培养阳性的病人随机进入雷贝拉唑联合克拉霉素与羟氨苄青霉素方案(RAC)或雷贝拉唑联合羟氨苄青霉素与甲硝唑方案(RAM)进行1周根除治疗。治疗前CYP2C19基因多态性通过PCR-限制性片段长度多态性进行鉴定,治疗结束至少4周后Hp的状态用”C-呼气试验进行检测。结果 在128例病人中纯合子强代谢型(hom-Ems)、杂合子强代谢型(het-Ems)、弱代谢型(PMs)分别为30．5％、50．0％、19．5％。在无克拉霉素、甲硝唑耐药菌株的情况下,RAC方案与RAM方案的Hp根除率分别为98．1％与91．3％(按治疗方案分析)。但是,甲硝唑的耐药率高达66．8％,降低了RAM方案的Hp根除率。logistic回归分析显示不同的CYP2C19基因型对Hp的根除率没有显著的影响。结论 以雷贝拉唑为基础的三联疗法根除Hp无明显个体差异,RAC的治疗方案值得推荐。

Effect of CYP2C19 genetic polymorphism on treatment efficacy of Helicobacter pylori infection with rabeprazole-based triple therapy in Chinese

OBJECTIVE: To investigate the effect of different S-mephenytoin 4'-hydroxylase (CYP2C19) genotype on the eradication rate of Helicobacter pylori (Hp) by different rabeprazole-based triple therapy in Chinese. METHODS: 128 subjects with Hp positive gastritis or peptic ulcers were randomly assigned to receive 10 mg rabeprazole twice daily with 1000 mg amoxicillin twice daily and 500 mg clarithromycin (RAC group) or 400 mg metronidazole (RAM group) twice daily for 1 week. The CYP2C19 genotype (homozygous extensive metabolizer, hom-Ems; heterozygous extensive metabolizer, het-Ems; or poor metabolizer, PMs) was determined by the polymerase chain reaction-restriction fragment length polymorphism method. More than 4 weeks after completion of treatment, Hp status was assessed by (13)C-urea breath test. RESULTS: The hom-Ems, het-Ems and PMs were 30.5%, 50.0% and 19.5% in 128 subjects, respectively. The eradication rates in the rabeprazole-amoxicillin-clarithromycin (RAC) for clarithromycin-sensitive strains and rabeprazole-amoxicillin-metronidazole (RAM) for metronidazole-sensitive strains groups were 98.1% and 91.3%, respectively, on a per protocol basis. It decreased significantly eradication rates of Hp because the prevalence of primary antimicrobial resistance was 66.8% for metronidazole. When the statistical significance of each parameter associated with treatment outcome was assessed with logistic regression analysis, CYP2C19 genetic polymorphism did not show significant effect on the efficacy of anti-Hp therapy with rabeprazole-based triple regimens. CONCLUSIONS: The efficacy of rabeprazole-based triple regimens is less affected by the CYP2C19 genotype, the RAC regimen can be considered in Chinese.