Micro-RNA as a new biomarker of activity of the cytochrome system P-450: significance for predicting the antiplatelet action of P2Y12 receptor inhibitors

Rytkin, Eric; Игоревич, Рыткин Эрик; Мирзаев, К. Б.; Бадавиевич, Мирзаев Карин; Bure, Irina V.; Владимировна, Буре Ирина; Сычев, Д. А.; Алексеевич, Сычев Дмитрий

doi:10.26442/00403660.2019.08.000389

Cited by 6 publications

(3 citation statements)

References 16 publications

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“…уровень которых коррелирует с экспрессией генов ферментов биотрансформации и транспортёров лекарственных средств и могут быть использованы как альтернатива фенотипированию этих систем [35]. Нами показана взаимосвязь между уровнем некоторых микро-РНК в плазме с антиагрегантным действие клопидогрела и тикагрелора у пациентов с острым коронарным синдромом (ОКС), концентрациями антидепрессантов у пациентов с алкогольной зависимостью [36].…”

Section: актуальные обзорыunclassified

Problems of integrating medical science, image and practical health care: focus on personalized medicine

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2020

Fgen_Fgenom

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On the example of technologies of personalization of pharmacotherapy based on biomarkers of the processes of absorption, distribution, metabolism and excretion of drugs (ADME-processes), the methodology of the results of scientific research into the educational process within the system of continuous medical education of doctors into the real clinical practice is presented. This methodology has been developed and implemented in the Russian Medical Academy of Continuing Professional Education.

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Section: актуальные обзорыunclassified

Problems of integrating medical science, image and practical health care: focus on personalized medicine

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2020

Fgen_Fgenom

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“…Micro-RNAs can be biomarkers for clopidogrel resistance through the ADME genes involved in the metabolism of clopidogrel. 27 In this article, we suggest six prospective microRNAs as potential biomarkers for guiding antiplatelet therapy among patients with ACS who have undergone PCI.…”

Section: Introductionmentioning

confidence: 99%

“…Micro-RNAs can be biomarkers for clopidogrel resistance through the ADME genes involved in the metabolism of clopidogrel. 27 …”

Section: Introductionmentioning

confidence: 99%

MicroRNAs as Novel Biomarkers for P2Y12 – Inhibitors Resistance Prediction

Rytkin¹,

Мирзаев²,

Bure³

et al. 2021

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The aim of this study is to assess 6 micro-RNAs: miR-126, miR-223, miR-150, miR-29, miR-34, miR-142 as potential biomarkers for P2Y12-inhibitors resistance prediction. Methods: Eighty patients with an acute coronary syndrome undergoing percutaneous coronary intervention treated in a multidisciplinary hospital in Moscow with DAPT (either with ticagrelor, n=45, or clopidogrel, n=35) were enrolled. The carriership of 6 clinically relevant polymorphisms for ticagrelor and 17 for clopidogrel was detected. Expression levels of six prospective miRNAs were measured. The activity of CYP3A4 isoenzyme was measured as the ratio of the concentrations of cortisol and 6β-hydroxycortisol. Results:The polymorphisms of the P2Y12-inhibitors ADME genes that demonstrated statistically significant connection with miRNA expression levels are as follows: P2Y12R (A>G, rs3732759) and miR-29 (p=0.017), miR-34 (p=0.003); CYP2C19*17 (C-806T, rs1224856) and miR-142 (p=0.012); PON1 (Q192R, rs662) and miR-29 (p=0.004), ABCG2 (G>T, rs2231142) and miR-34 (p=0.007). MiRNAs expression levels showed connection with the results of the platelet reactivity assessment by utilizing VerifyNow assay ("Instrumentation laboratory", MA, US). MiR-126 (β coefficient=−0.076, SE=0.032, p=0.021), miR-223 (β coefficient=−0.089, SE=0.041, p=0.032), miR-29 (β coefficient=−0.042, SE=0.018, p=0.026), miR-142 (β coefficient=−0.072, SE=0.026, p=0.008) have the potential to be used as biomarkers and may substitute platelet reactivity testing. Conclusion:This study has revealed new biomarkers for P2Y12-inhibitors resistance testing: miR-29, miR-34, miR-126, miR-142, miR-223.

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MicroRNAs as novel biomarkers for rivaroxaban therapeutic drug monitoring

Rytkin

Bure

Бочков

et al. 2021

Drug Metabolism and Personalized Therapy

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Objectives The aim of this study is to assess micro-RNAs miR-142 and miR-39 as potential biomarkers for drug-monitoring of rivaroxaban among elderly patients with atrial fibrillation. Methods The study involved 57 patients with median (ME) age 87 years [80–94 years old] with nonvalvular atrial fibrillation admitted to a multidisciplinary hospital in Moscow. High-performance liquid chromatography with mass-spectrometry detection (HPLC-MS) was carried out to measure rivaroxaban concentrations. Carriership of CYP3A4 and ABCB1 was detected. MiRNA expression levels were measured. The activity of CYP3A4 isoenzyme was measured as the ratio of the concentrations of 6β-hydroxycortisol and cortisol. Results The miR-142 expression levels of patients with CC allelic variant polymorphism ABCB1 3435 C>T (rs1045642) were significantly higher compared to CT and TT variants 31.69 ± 1.60 vs. 34.06 ± 1.66 vs. 33.16 ± 1.77 (p=0.021). Carriers of TT allelic variant polymorphism ABCB1 rs4148738 had a higher concentration of the 6-beta-hydroxycortisol in urine compared to CC and CT variants 3,467.35 ± 1,055.53 vs. 3,453.52 ± 1,516.89 vs. 2,593.30 ± 1,172.52 (p=0.029). As for CYP3A4*22, the carriers of CC allelic variant had higher prothrombin time 14.10 ± 2.17 vs. 11.87 ± 0.60 and INR 1.31 ± 0.20 vs. 1.1 ± 0.06 but lower Quick’s value 74.52 ± 16.84 vs. 97.55 ± 10.54 (p=0.059). A positive correlation between the Ct miR-142 and the aPTT p=0.019 was noted. Also miR-142 has a correlation with Quick’s value p=0.095. There is no statistically significant connection between miR-142 and miR-39 expression levels and the plasma concentration of rivaroxaban (b coefficient=−2.055, SE 3.952, p=0.605 and b coefficient=1.546, SE 9.887, p=0.876 in the linear regression model respectively). Conclusions This study has assessed new potential biomarkers for rivaroxaban therapeutic drug monitoring: miR-142 and miR-39.

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Micro-RNA as a new biomarker of activity of the cytochrome system P-450: significance for predicting the antiplatelet action of P2Y12 receptor inhibitors

Cited by 6 publications

References 16 publications

Problems of integrating medical science, image and practical health care: focus on personalized medicine

Problems of integrating medical science, image and practical health care: focus on personalized medicine

MicroRNAs as Novel Biomarkers for P2Y12 – Inhibitors Resistance Prediction

MicroRNAs as novel biomarkers for rivaroxaban therapeutic drug monitoring

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