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ABCB1、CYP2B6 和 CYP3A4 基因多态性不影响 HCV 阳性患者的美沙酮维持治疗。

ABCB1, CYP2B6, and CYP3A4 genetic polymorphisms do not affect methadone maintenance treatment in HCV-positive patients.

机构信息

University of Split, Department for Health Studies, Split, Croatia.

University of Split School of Medicine, Department of Toxicology and Pharmacogenetics, Split, Croatia.

出版信息

Arh Hig Rada Toksikol. 2020 Dec 31;71(4):353-358. doi: 10.2478/aiht-2020-71-3378.

Abstract

The aim of this study was to determine the influence of ABCB1, CYP2B6, and CYP3A4 genetic polymorphisms on methadone metabolism in patients with hepatitis C virus (HCV) undergoing methadone maintenance treatment (MMT). The study included 35 participants undergoing MMT, who were divided in three groups: HCV-positive (N=12), HCV-negative (N=16), and HCV clinical remission (CR) (N=7). The concentrations of methadone and its main metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) were determined with gas chromatography-mass spectrometry. The patients were genotyped for ABCB1 rs1045642, CYP2B6 rs3745274, CYP3A4 rs2242480, and CYP3A4 rs2740574 polymorphisms. Differences between single nucleotide polymorphism (SNP) genotypes and methadone-to-EDDP ratio were analysed with one-way ANOVA, which showed no significant difference between the genes (p=0.3772 for ABCB1 rs1045642, p=0.6909 for CYP2B6 rs3745274, and p=0.6533 for CYP3A4 rs2242480). None of the four analysed SNP genotypes correlated with methadone-to-EDDP concentration ratio. A major influence on it in hepatitis C-positive patients turned out to be the stage of liver damage.

摘要

本研究旨在确定 ABCB1、CYP2B6 和 CYP3A4 基因多态性对丙型肝炎病毒 (HCV) 接受美沙酮维持治疗 (MMT) 的患者中美沙酮代谢的影响。该研究纳入了 35 名接受 MMT 的患者,他们分为三组:HCV 阳性 (N=12)、HCV 阴性 (N=16) 和 HCV 临床缓解 (CR) (N=7)。采用气相色谱-质谱法测定美沙酮及其主要代谢物 2-亚乙基-1,5-二甲基-3,3-二苯基吡咯烷 (EDDP) 的浓度。对患者进行 ABCB1 rs1045642、CYP2B6 rs3745274、CYP3A4 rs2242480 和 CYP3A4 rs2740574 基因多态性检测。采用单因素方差分析 (ANOVA) 分析单核苷酸多态性 (SNP) 基因型与美沙酮-EDDP 比值之间的差异,结果显示基因之间无显著差异 (ABCB1 rs1045642 的 p=0.3772,CYP2B6 rs3745274 的 p=0.6909,CYP3A4 rs2242480 的 p=0.6533)。分析的四种 SNP 基因型均与美沙酮-EDDP 浓度比值无关。丙型肝炎阳性患者的主要影响因素是肝损伤的阶段。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9990/7968507/7d248bb83b5e/aiht-71-353-g001.jpg

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