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Circulating miRNAs as Biomarkers for CYP2B6 Enzyme Activity
Joseph Ipe1, Rudong Li2, Ingrid F Metzger1,2
1Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Clinical Pharmacology and Therapeutics
|August 11, 2020
Summary
Circulating microRNAs (miRNAs) can predict cytochrome P450 2B6 (CYP2B6) enzyme activity. This study identified 7 miRNAs that, with genetic and demographic data, explain 36% of CYP2B6 activity variability.
Area of Science:
- Pharmacogenomics
- Biomarker Discovery
- Molecular Biology
Background:
- Cytochrome P450 2B6 (CYP2B6) exhibits significant interindividual activity variability.
- Known genetic variations do not fully explain CYP2B6 activity differences.
- Circulating microRNAs (miRNAs) are potential biomarkers for hepatic enzyme activity.
Purpose of the Study:
- To investigate circulating miRNAs as predictive biomarkers for in vivo CYP2B6 activity.
- To develop a model incorporating miRNA expression, genotype, and demographics to predict CYP2B6 activity.
Main Methods:
- CYP2B6 activity was assessed in 72 healthy volunteers using efavirenz as a probe drug.
- Plasma miRNA expression profiling was performed on baseline samples.
- A linear model was built using miRNA expression, CYP2B6 genotype, and demographic data to predict CYP2B6 activity.
Main Results:
- A model including 7 miRNAs, CYP2B6 metabolizer status, and demographics predicted efavirenz Cmax ratios with a Pearson correlation (R) of 0.6702.
- The model explained 36% (R^2) of the variability in in vivo CYP2B6 activity.
- This model significantly outperformed models using only genotype or demographics (which explained ≤6% variability).
Conclusions:
- Circulating plasma miRNAs are valuable biomarkers for predicting in vivo CYP2B6 activity.
- Integrating miRNA expression with genetic and demographic data enhances the prediction of drug-metabolizing enzyme activity.
- This approach offers improved understanding and prediction of pharmacogenetic variability.
