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[幽门螺杆菌根除疗效取决于细胞色素P450 2C19、多药耐药蛋白1及白细胞介素-1β的基因多态性]

[Efficacy of H. pylori eradication depending on genetic polymorphism of CYP2C19, MDR1 and IL-1β].

作者信息

Bakulina N V, Maev I V, Savilova I V, Bakulin I G, Il'chishina T A, Zagorodnikova K A, Murzina A A, Andreev D N

机构信息

Mechnikov North-Western State Medical University.

Yevdokimov Moscow State University of Medicine and Dentistry.

出版信息

Ter Arkh. 2019 Aug 15;91(8):34-40. doi: 10.26442/00403660.2019.08.000380.

Abstract

AIM

To evaluate an association of genetic polymorphisms CYP2C19, MDR1, and IL-1β on the eradication rate by 10-day modified therapy in patients with H. pylori - associated diseases.

MATERIALS AND METHODS

In this study was conducted a prospective, randomized trial, included 89 patients with H. pylori - associated diseases. They were divided into 2 groups depending on therapy: clarithromycin 500 mg, b.i.d., amoxicillin 1000 mg, b.i.d., bismuth subcitrate 240 mg, b.i.d. rabeprazole 20 mg or 40 mg, b.i.d. for 10 days. All subjects underwent pharmacogenetic testing of CYP2C19, MDR1, and IL-1β.

RESULTS AND DISCUSSION

Per - protocol (PP) eradication rates in group with rabeprazole 40 mg were 97.6% (41/42; 95% CI 87.7-99.6), in group with rabeprazole 20 mg were 82.1% (32/39; 95% CI 67.3-91.0). Intention - to - treat analysis in group with rabeprazole 40 mg eradication rates were 89.1% (41/46; 95% CI 77.0-95.3), in group with standard dose rabeprazole - 74.4% (32/43; 95% CI 59.8-85.1). No significant differences in eradication rates between the groups of ultrarapid, rapid, normal and intermediate CYP2C19 metabolizers (PP: 93.5%/90.3%/84.6% respectively; χ2=0.87, p=0.65). Eradication rates in group with IL-1β CC genotype there was no difference among the IL-1β CT and TT genotype groups (PP: 92.9%/85.7%/94.7% respectively; χ2=1.34; p=0.51). The cure rate among MDR1 TT genotype was significantly lower than among subjects in the MDR1 CC/CT genotype groups (PP: 76.2% vs 96.3%: χ2=5.04; p=0.025; OR=8.13).

CONCLUSION

Ten - day modified triple therapy with high dose rabeprazole significantly high eradication rates in patients with H. pylori - associated diseases. Independent factor for treatment failure is MDR1 CC/CT genotype status.

摘要

目的

评估细胞色素P450 2C19(CYP2C19)、多药耐药基因1(MDR1)和白细胞介素-1β(IL-1β)的基因多态性与幽门螺杆菌相关疾病患者接受10天改良疗法后的根除率之间的关联。

材料与方法

本研究进行了一项前瞻性随机试验,纳入89例幽门螺杆菌相关疾病患者。根据治疗方法将他们分为2组:克拉霉素500毫克,每日2次;阿莫西林1000毫克,每日2次;枸橼酸铋钾240毫克,每日2次;雷贝拉唑20毫克或40毫克,每日2次,共10天。所有受试者均接受了CYP2C19、MDR1和IL-1β的药物遗传学检测。

结果与讨论

雷贝拉唑40毫克组的符合方案(PP)根除率为97.6%(41/42;95%可信区间87.7 - 99.6),雷贝拉唑20毫克组为82.1%(32/39;95%可信区间67.3 - 91.0)。雷贝拉唑40毫克组的意向性治疗分析根除率为89.1%(41/46;95%可信区间77.0 - 95.3),标准剂量雷贝拉唑组为74.4%(32/43;95%可信区间59.8 - 85.1)。超快、快速、正常和中间型CYP2C19代谢者组之间的根除率无显著差异(PP:分别为93.5%/90.3%/84.6%;χ2 = 0.87,p = 0.65)。IL-1β CC基因型组的根除率与IL-1β CT和TT基因型组之间无差异(PP:分别为92.9%/85.7%/94.7%;χ2 = 1.34;p = 0.51)。MDR1 TT基因型的治愈率显著低于MDR1 CC/CT基因型组的受试者(PP:76.2%对96.3%:χ2 = 5.04;p = 0.025;比值比 = 8.13)。

结论

高剂量雷贝拉唑的10天改良三联疗法在幽门螺杆菌相关疾病患者中具有显著高的根除率。治疗失败的独立因素是MDR1 CC/CT基因型状态。

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