Effects of plasma concentration of micro-RNA Mir-27b and CYP3A4*22 on equilibrium concentration of alprazolam in patients with anxiety disorders comorbid with alcohol use disorder

Застрожин, Михаил Сергеевич; Skryabin, Valentin Yurievich; Смирнов, В. В.; Петухов, А. Е.; Pankratenko, E. P.; Zastrozhina, A.K.; Grishina, Elena A.; Рыжикова, К. А.; Bure, Irina V.; Golovinskii, Pavel; Koporov, Sergey; Bryun, Evgeny А.; Сычев, Д. А.

doi:10.1016/j.gene.2020.144513

Cited by 12 publications

(9 citation statements)

References 15 publications

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“…1 and 2 , both miR-27b-3p, miR-320b have multiple targets that can have modulatory effects on brain function. This is consistent with findings from case–control studies in anxiety or depression showing evidence for an increase in miRs including miR-27b-3 41 and miR-320b 20 , which has been more closely related to metabolic dysfunction 42 , 43 . For example, global upregulation of miR-320 has been associated with impaired gluconeogenesis, lipid metabolism, and relatively higher expression of inflammation markers 44 .…”

Section: Discussionsupporting

confidence: 90%

Neuronally-enriched exosomal microRNA-27b mediates acute effects of ibuprofen on reward-related brain activity in healthy adults: a randomized, placebo-controlled, double-blind trial

Burrows

Figueroa-Hall

Kuplicki

et al. 2022

Sci Rep

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This double-blind, randomized, within-subjects design evaluated whether acute administration of an anti-inflammatory drug modulates neuron-specific, inflammation-modulating microRNAs linked to macroscopic changes in reward processing. Twenty healthy subjects (10 females, 10 males) underwent a functional magnetic resonance imaging scan while performing a monetary incentive delay (MID) task and provided blood samples after administration of placebo, 200 mg, or 600 mg of ibuprofen. Neuronally-enriched exosomal microRNAs were extracted from serum and sequenced. Results showed that: (1) 600 mg of ibuprofen exhibited higher miR-27b-3p, miR-320b, miR-23b and miR-203a-3p expression than placebo; (2) higher mir-27b-3p was associated with lower insula activation during MID loss anticipation; and (3) there was an inverse relationship between miR-27b-3p and MID gain anticipation in bilateral putamen during placebo, a pattern attenuated by both 200 mg and 600 mg of ibuprofen. These findings are consistent with the hypothesis that miR-27b could be an important messaging molecule that is associated with regulating the processing of positive or negative valenced information.

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Section: Discussionsupporting

confidence: 90%

Neuronally-enriched exosomal microRNA-27b mediates acute effects of ibuprofen on reward-related brain activity in healthy adults: a randomized, placebo-controlled, double-blind trial

Burrows

Figueroa-Hall

Kuplicki

et al. 2022

Sci Rep

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“…In a recent study of 105 male patients with alprazolam treatment due to anxiety disorder, a significant association was found between 6β‐OHC/C and miRNA‐27b 61 . However, there was no association between 6β‐OHC/C and miRNA‐27b in this study.…”

Section: Discussioncontrasting

confidence: 83%

“…In a recent study of 105 male patients with alprazolam treatment due to anxiety disorder, a significant association was found between 6β‐OHC/C and miRNA‐27b. 61 However, there was no association between 6β‐OHC/C and miRNA‐27b in this study. This may be due to differences between the sexes or to the different roles miRNAs may have in biological functions and diseases.…”

Section: Discussioncontrasting

confidence: 63%

Studies on CYP3A activity during the menstrual cycle as measured by urinary 6β‐hydroxycortisol/cortisol

Bergström

Lindahl

Warnqvist

et al. 2021

Pharmacology Res & Perspec

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The 6β‐OH‐cortisol/cortisol ratio (6β‐OHC/C) in urine is an endogenous marker of drug‐metabolizing enzyme cytochrome P450 3A (CYP3A). The primary aim of this single center, prospective, non‐interventional cohort study, was to investigate the variability of 6β‐OHC/C during the menstrual cycle. In addition, possible associations between the CYP3A activity and sex hormones, gut microbiota metabolite trimethylamine‐N‐Oxide (TMAO) and microRNA‐27b, respectively, were investigated. Serum and urinary samples from healthy, regularly menstruating women followed for two menstrual cycles were analyzed. Twenty‐six complete menstrual cycles including follicular, ovulatory, and luteal phase were defined based on hormone analyses in serum. 6β‐OHC/C were analyzed in urine and sex hormones, TMAO and miRNA‐27b were analyzed in serum at the same time points. 6β‐OHC/C did not vary between the follicular, ovulatory, or luteal phases. There was a difference in the relative miRNA‐27b expression between the follicular and ovulatory phase ( p = .03). A significant association was found between 6β‐OHC/C and progesterone during the follicular ( p = .005) and ovulatory ( p = .01) phases ( n = 26 for each phase). In addition, a significant association was found between the ratio and TMAO during the ovulatory ( p = .02) and luteal ( p = .002) phases. 6β‐OHC/C and gut microbiota TMAO were significantly associated ( p = .003) when evaluating all values, for all phases ( n = 78). Interestingly, the finding of an association between 6β‐OHC/C in urine and levels of TMAO in serum suggest that gut microbiota may affect CYP3A activity.

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“…Alprazolam is one of the most commonly prescribed psychoactive agent for mood and anxiety disorders ( Stahl, 2002 ). In patients with alcoholism and anxiety disorders, CYP3A4 ∗ 22 carriers had significantly increased active alprazolam concentration/dose ratios and a decreased treatment response, as reflected in HAMA scale scores (4.0 vs. 3.0) ( Zastrozhin et al, 2020 ) ( Supplementary Table 4 ).…”

Section: Psychiatrymentioning

confidence: 99%

CYP3A4∗22 Genotyping in Clinical Practice: Ready for Implementation?

et al. 2021

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Cytochrome P450 3A4 (CYP3A4) is the most important drug metabolizing enzyme in the liver, responsible for the oxidative metabolism of ∼50% of clinically prescribed drugs. Therefore, genetic variation in CYP3A4 could potentially affect the pharmacokinetics, toxicity and clinical outcome of drug treatment. Thus far, pharmacogenetics for CYP3A4 has not received much attention. However, the recent discovery of the intron 6 single-nucleotide polymorphism (SNP) rs35599367C > T, encoding the CYP3A4∗22 allele, led to several studies into the pharmacogenetic effect of CYP3A4∗22 on different drugs. This allele has a relatively minor allele frequency of 3-5% and an effect on CYP3A4 enzymatic activity. Thus far, no review summarizing the data published on several drugs is available yet. This article therefore addresses the current knowledge on CYP3A4∗22. This information may help in deciding if, and for which drugs, CYP3A4∗22 genotype-based dosing could be helpful in improving drug therapy. CYP3A4∗22 was shown to significantly influence the pharmacokinetics of several drugs, with currently being most thoroughly investigated tacrolimus, cyclosporine, and statins. Additional studies, focusing on toxicity and clinical outcome, are warranted to demonstrate clinical utility of CYP3A4∗22 genotype-based dosing.

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Effects of plasma concentration of micro-RNA Mir-27b and CYP3A4*22 on equilibrium concentration of alprazolam in patients with anxiety disorders comorbid with alcohol use disorder

Cited by 12 publications

References 15 publications

Neuronally-enriched exosomal microRNA-27b mediates acute effects of ibuprofen on reward-related brain activity in healthy adults: a randomized, placebo-controlled, double-blind trial

Neuronally-enriched exosomal microRNA-27b mediates acute effects of ibuprofen on reward-related brain activity in healthy adults: a randomized, placebo-controlled, double-blind trial

Studies on CYP3A activity during the menstrual cycle as measured by urinary 6β‐hydroxycortisol/cortisol

CYP3A4∗22 Genotyping in Clinical Practice: Ready for Implementation?

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