Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, Turin, Italy.
Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, Turin, Italy.
Infect Genet Evol. 2018 Jun;60:42-47. doi: 10.1016/j.meegid.2018.02.016. Epub 2018 Feb 13.
Vitamin D levels and genetic variants were associated with drug outcome/toxicity and concentrations. The plasma exposure of GS-331007, the main sofosbuvir metabolite, has been related to SVR. We evaluated the impact of polymorphisms in genes (CYP27B1, CYP24A1, VDBP and VDR) related to vitamin D pathway on sofosbuvir and GS-331007 plasma levels in HCV mono-infected patients at one month of treatment. Polymorphisms were investigated through real-time PCR; drug plasma quantification was performed through a UHPLC-MS/MS method. GS-331007 levels were associated with CYP24A1rs2248359 and VDRCdx2 variants in all the analyzed patients and linear regression analysis showed that sex, body mass index, HCV genotype, baseline estimated glomerular filtration rate, VDRCdx2AG/GG and CYP27B1-1260TT genotypes significantly predict concentrations. We performed sub-analyses considering the HCV genotype and the concomitant drug, identifying polymorphisms associated with GS-331007 concentrations. This is the first study focusing on vitamin D pathway gene variants and DAAs concentrations, but further studies are required.
维生素 D 水平和遗传变异与药物疗效/毒性和浓度有关。GS-331007（主要的索磷布韦代谢物）的血浆暴露与 SVR 有关。我们评估了与维生素 D 途径相关的基因（CYP27B1、CYP24A1、VDBP 和 VDR）中的多态性对 HCV 单感染患者治疗 1 个月时索磷布韦和 GS-331007 血浆水平的影响。通过实时 PCR 研究多态性；通过 UHPLC-MS/MS 方法进行药物血浆定量。在所有分析的患者中，GS-331007 水平与 CYP24A1rs2248359 和 VDRCdx2 变异有关，线性回归分析表明，性别、体重指数、HCV 基因型、基线估计肾小球滤过率、VDRCdx2AG/GG 和 CYP27B1-1260TT 基因型显著预测浓度。我们进行了亚分析，考虑了 HCV 基因型和伴随药物，确定了与 GS-331007 浓度相关的多态性。这是第一项关注维生素 D 途径基因变异和 DAA 浓度的研究，但需要进一步研究。
