TY - JOUR
T1 - Vitamin D pathway genetic variants are able to influence sofosbuvir and its main metabolite pharmacokinetics in HCV mono-infected patients
AU - Cusato, Jessica
AU - De Nicolò, Amedeo
AU - Boglione, Lucio
AU - Favata, Fabio
AU - Ariaudo, Alessandra
AU - Mornese Pinna, Simone
AU - Carcieri, Chiara
AU - Guido, Federica
AU - Avataneo, Valeria
AU - Cariti, Giuseppe
AU - Di Perri, Giovanni
AU - D'Avolio, Antonio
N1 - Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2018/6
Y1 - 2018/6
N2 - 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.
AB - 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.
KW - Calcitriol
KW - Chronic hepatitis C
KW - DAA
KW - Pharmacogenetics
KW - SNP
KW - Therapeutic drug monitoring
UR - http://www.scopus.com/inward/record.url?scp=85042268615&partnerID=8YFLogxK
U2 - 10.1016/j.meegid.2018.02.016
DO - 10.1016/j.meegid.2018.02.016
M3 - Article
SN - 1567-1348
VL - 60
SP - 42
EP - 47
JO - Infection, Genetics and Evolution
JF - Infection, Genetics and Evolution
ER -
