Your browser doesn't support javascript.
loading
Circulating miRNAs as Biomarkers for CYP2B6 Enzyme Activity.
Ipe, Joseph; Li, Rudong; Metzger, Ingrid F; Bo Li Lu, Jessica; Gufford, Brandon T; Desta, Zeruesenay; Liu, Yunlong; Skaar, Todd C.
Affiliation
  • Ipe J; Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
  • Li R; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
  • Metzger IF; Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
  • Bo Li Lu J; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
  • Gufford BT; Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
  • Desta Z; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
  • Liu Y; Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
  • Skaar TC; Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Clin Pharmacol Ther ; 109(2): 485-493, 2021 02.
Article in En | MEDLINE | ID: mdl-32772362
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 (Cmax ) ratios of efavirenz and its metabolite-8-OH efavirenz using the linear model with all features (7 miRNA + metabolizer status + age + sex + race) was 0.6702. Similar results were also observed using area under the curve (AUC) ratios (Pearson correlation's R = 0.6035). Thus, at least 36% (R2 ) of the variability of in vivo CYP2B6 activity was explained using this model. This is a significant improvement over the models using only the genotype-based metabolizer status or the demographic information, which explained only 6% or less of the variability of in vivo CYP2B6 activity. Our results, therefore, demonstrate that circulating plasma miRNAs can be valuable biomarkers for in vivo CYP2B6 activity.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Biomarkers / MicroRNAs / Cytochrome P-450 CYP2B6 Type of study: Prognostic_studies Limits: Adolescent / Adult / Female / Humans / Male / Middle aged Language: En Journal: Clin Pharmacol Ther Year: 2021 Document type: Article Affiliation country: United States Country of publication: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Biomarkers / MicroRNAs / Cytochrome P-450 CYP2B6 Type of study: Prognostic_studies Limits: Adolescent / Adult / Female / Humans / Male / Middle aged Language: En Journal: Clin Pharmacol Ther Year: 2021 Document type: Article Affiliation country: United States Country of publication: United States