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

Author:

Sutlović Davorka12,Ključević Željko3,Kuret Sendi14

Affiliation:

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

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

3. Public Health Institute of the Split-Dalmatia County , Department of Mental Health, Prevention and Outpatient Addiction Treatment , Split , Croatia

4. University Hospital Centre Split , Department of Pathology and Forensic Medicine , Split , Croatia

Abstract

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.

Publisher

Walter de Gruyter GmbH

Subject

Public Health, Environmental and Occupational Health,Toxicology

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