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利福喷丁和异烟肼治疗潜伏性结核病患者中药物代谢酶遗传多态性与药物不良反应的关系。

Association of Drug Metabolic Enzyme Genetic Polymorphisms and Adverse Drug Reactions in Patients Receiving Rifapentine and Isoniazid Therapy for Latent Tuberculosis.

机构信息

Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.

Department of Clinical Laboratory, Changhua Hospital, Changhua 513, Taiwan.

出版信息

Int J Environ Res Public Health. 2019 Dec 27;17(1):210. doi: 10.3390/ijerph17010210.

Abstract

Weekly rifapentine and isoniazid therapy (3HP) is the most frequent treatment for latent tuberculosis infection (LTBI). However, the association between major adverse drug reactions (ADRs) and drug metabolic enzyme single-nucleotide polymorphisms (SNPs) remains unclear. In this study, 377 participants who received the 3HP regimen were recruited and examined for genotyping of CYP5A6, CYP2B6, CYP2C19, CYP2E1, and NAT2 SNPs. In our study, 184 participants (48.4%) developed ADRs. Moreover, CYP2C19 rs4986893 (TT vs. CC+CT, odds ratio [OR] [95% CI]: 2.231 [1.015-4.906]), CYP2E1 rs2070676 (CC vs. CG+GG, OR [95% CI]: 1.563 [1.022-2.389]), and CYP2E1 rs2515641 (CC vs. CT+TT, OR [95% CI]: 1.903 [1.250-2.898]) were associated with ADR development. In conclusion, CYP2C19 and CYP2E1 SNPs may provide useful information regarding ADRs in LTBI patients receiving the 3HP regimen.

摘要

每周利福喷丁和异烟肼疗法(3HP)是治疗潜伏性结核感染(LTBI)最常用的方法。然而,主要药物不良反应(ADR)与药物代谢酶单核苷酸多态性(SNP)之间的关联尚不清楚。在这项研究中,招募了 377 名接受 3HP 方案治疗的参与者,并对 CYP5A6、CYP2B6、CYP2C19、CYP2E1 和 NAT2 SNPs 进行了基因分型检测。在我们的研究中,184 名参与者(48.4%)发生了 ADR。此外,CYP2C19 rs4986893(TT 与 CC+CT,比值比[OR] [95%置信区间]:2.231 [1.015-4.906])、CYP2E1 rs2070676(CC 与 CG+GG,OR [95%置信区间]:1.563 [1.022-2.389])和 CYP2E1 rs2515641(CC 与 CT+TT,OR [95%置信区间]:1.903 [1.250-2.898])与 ADR 发生相关。总之,CYP2C19 和 CYP2E1 SNP 可能为接受 3HP 方案治疗的 LTBI 患者的 ADR 提供有用的信息。

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