Vitamin D pathway gene polymorphisms affecting daclatasvir plasma concentration at 2 weeks and 1 month of therapy.

ABSTRACT

AIM: Vitamin D (VD) influences genetic expression through its receptor (VDR). VD pathway gene polymorphisms seem to influence antiviral drug pharmacokinetics and therapeutic outcome/toxicity. We investigated the association between daclatasvir (DCV) plasma concentrations and genetic variants (SNPs) associated with the VD pathway. PATIENTS & METHODS: Chronic hepatitis C patients treated with DCV from 2014 to 2016 were included. Genotypes were assessed through real-time PCR and plasma concentrations through liquid chromatography. RESULTS: A total of 52 patients were analyzed. DCV levels were influenced by CYP24A1 rs2248359T>C polymorphism at 2 weeks and VDR Cdx2 A>G at 1 month of treatment. Linear regression analysis showed baseline BMI, alanine aminotransferase and hematocrit as significant predictors of DCV concentrations at 2 weeks, BMI and hematocrit at baseline, VDR Cdx2 AG/GG and FokI TC/CC at 1 month. CONCLUSION: These results showed a possible role of VD pathway gene polymorphisms in influencing DCV plasma concentrations, but further studies are required.