Circulating miRNAs as Biomarkers for CYP2B6 Enzyme Activity.
Adolescent
Adult
Alkynes
/ therapeutic use
Anti-HIV Agents
/ therapeutic use
Benzoxazines
/ therapeutic use
Biomarkers
/ blood
Cyclopropanes
/ therapeutic use
Cytochrome P-450 CYP2B6
/ genetics
Female
Genotype
Humans
Male
MicroRNAs
/ blood
Middle Aged
Polymorphism, Genetic
/ genetics
Reproducibility of Results
Young Adult
Journal
Clinical pharmacology and therapeutics
ISSN: 1532-6535
Titre abrégé: Clin Pharmacol Ther
Pays: United States
ID NLM: 0372741
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
04
02
2020
accepted:
16
07
2020
pubmed:
11
8
2020
medline:
22
5
2021
entrez:
11
8
2020
Statut:
ppublish
Résumé
The CYP2B6 gene is highly polymorphic and its activity shows wide interindividual variability. However, substantial variability in CYP2B6 activity remains unexplained by the known CYP2B6 genetic variations. Circulating, cell-free micro RNAs (miRNAs) may serve as biomarkers of hepatic enzyme activity. CYP2B6 activity in 72 healthy volunteers was determined using the disposition of efavirenz as a probe drug. Circulating miRNA expression was quantified from baseline plasma samples. A linear model consisting of the effects of miRNA expression, genotype-determined metabolizer status, and demographic information was developed to predict CYP2B6 activity. Expression of 2,510 miRNAs were quantified out of which 7 miRNAs, together with the CYP2B6-genotypic metabolizer status and demographics, was shown to be predictive markers for CYP2B6 activity. The reproducibility of the model was evaluated by cross-validation. The average Pearson's correlation (R) between the predicted and observed maximum plasma concentration (C
Identifiants
pubmed: 32772362
doi: 10.1002/cpt.2018
pmc: PMC9007394
mid: NIHMS1683365
doi:
Substances chimiques
Alkynes
0
Anti-HIV Agents
0
Benzoxazines
0
Biomarkers
0
Cyclopropanes
0
MicroRNAs
0
CYP2B6 protein, human
EC 1.14.14.1
Cytochrome P-450 CYP2B6
EC 1.14.14.1
efavirenz
JE6H2O27P8
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
485-493Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM078501
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM121707
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM131812
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008425
Pays : United States
Informations de copyright
© 2020 The Authors Clinical Pharmacology & Therapeutics © 2020 American Society for Clinical Pharmacology and Therapeutics.
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