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  • Title: ABCB1, CYP2B6, and CYP3A4 genetic polymorphisms do not affect methadone maintenance treatment in HCV-positive patients.
    Author: Sutlović D, Ključević Ž, Kuret S.
    Journal: Arh Hig Rada Toksikol; 2020 Dec 31; 71(4):353-358. PubMed ID: 33410778.
    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. Cilj ovoga istraživanja bio je utvrditi utjecaj polimorfizama gena ABCB1, CYP2B6 i CYP3A4 na metabolizam metadona u bolesnika/ovisnika s pozitivnim nalazom virusa hepatitisa C (HCV) na metadonskoj terapiji održavanja. Istraživanje je provedeno na uzorku od 35 sudionika na metadonskoj terapiji održavanja, podijeljenih u sljedeće skupine: HCV pozitivni (N=12), HCV negativni (N=16) i oni s kliničkom remisijom HCV-a (CR) (N=7). Koncentracije metadona i njegova glavnog metabolita 2-etiliden-1,5-dimetil-3,3-difenilpirolidina (EDDP) utvrđene su plinskom kromatografijom – masenom spektrometrijom. U sudionika su analizirani genski polimorfizmi ABCB1 rs1045642, CYP2B6 rs3745274, CYP3A4 rs2242480 i CYP3A4 rs2740574. Jednosmjerna analiza varijance (engl. one-way ANOVA) nije pokazala statistički značajne razlike između genotipova jednonukleotidnih polimorfizama (engl. single-nucleotide polymorphism, krat. SNP) u omjeru koncentracije metadona i EDDP-a (p=0,3772 za ABCB1 rs1045642; p=0,6909 za CYP2B6 rs3745274 F=0,374 i p=0,6533 za CYP3A4 rs2242480). Nijedan od četiriju analiziranih SNP genotipova nije korelirao s omjerom koncentracije metadona i EDDP-a. U bolesnika/ovisnika koji su bili pozitivni na HCV na taj je omjer ponajviše utjecao stupanj oštećenja jetre.
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