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

Jessica Cusato; Amedeo De Nicolò; Lucio Boglione; Fabio Favata; Alessandra Ariaudo; Simone Mornese Pinna; Chiara Carcieri; Federica Guido; Giuseppe Cariti; Giovanni Di Perri; Antonio D'Avolio

doi:10.2217/pgs-2018-0009

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

Jessica Cusato, Amedeo De Nicolò, Lucio Boglione, Fabio Favata, Alessandra Ariaudo, Simone Mornese Pinna, Chiara Carcieri, Federica Guido, Giuseppe Cariti, Giovanni Di Perri, Antonio D'Avolio

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	701-706
Number of pages	6
Journal	Pharmacogenomics
Volume	19
Issue number	8
DOIs	https://doi.org/10.2217/pgs-2018-0009
Publication status	Published - 2018
Externally published	Yes

Keywords

CYP24A1
DAAs
SNP
VDR
pharmacogenetics
pharmacokinetics

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.2217/pgs-2018-0009

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@article{5e7116cac15641a8a89971cca5ae4e1b,

title = "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.",

keywords = "CYP24A1, DAAs, SNP, VDR, pharmacogenetics, pharmacokinetics",

author = "Jessica Cusato and Nicol{\`o}, {Amedeo De} and Lucio Boglione and Fabio Favata and Alessandra Ariaudo and Pinna, {Simone Mornese} and Chiara Carcieri and Federica Guido and Giuseppe Cariti and Perri, {Giovanni Di} and Antonio D'Avolio",

note = "Publisher Copyright: {\textcopyright} 2018 Future Medicine Ltd.",

year = "2018",

doi = "10.2217/pgs-2018-0009",

language = "English",

volume = "19",

pages = "701--706",

journal = "Pharmacogenomics",

issn = "1462-2416",

publisher = "Taylor and Francis Ltd.",

number = "8",

}

TY - JOUR

T1 - Vitamin D pathway gene polymorphisms affecting daclatasvir plasma concentration at 2 weeks and 1 month of therapy

AU - Cusato, Jessica

AU - Nicolò, Amedeo De

AU - Boglione, Lucio

AU - Favata, Fabio

AU - Ariaudo, Alessandra

AU - Pinna, Simone Mornese

AU - Carcieri, Chiara

AU - Guido, Federica

AU - Cariti, Giuseppe

AU - Perri, Giovanni Di

AU - D'Avolio, Antonio

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - CYP24A1

KW - DAAs

KW - SNP

KW - VDR

KW - pharmacogenetics

KW - pharmacokinetics

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U2 - 10.2217/pgs-2018-0009

DO - 10.2217/pgs-2018-0009

M3 - Article

SN - 1462-2416

VL - 19

SP - 701

EP - 706

JO - Pharmacogenomics

JF - Pharmacogenomics

IS - 8

ER -

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

Abstract

Keywords

UN SDGs

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