University of Split, Department for Health Studies, Split, Croatia.
University of Split School of Medicine, Department of Toxicology and Pharmacogenetics, Split, Croatia.
Arh Hig Rada Toksikol. 2020 Dec 31;71(4):353-358. doi: 10.2478/aiht-2020-71-3378.
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.
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。