MicroRNAs as Novel Biomarkers for P2Y12 – Inhibitors Resistance Prediction

Eric Rytkin,1 Karin Mirzaev,1 Irina Bure,1 Kristina Akmalova,1 Sherzod Abdullaev,1 Anastasiia Kachanova,1 Valery Smirnov,2,3 Elena Grishina,1 Natalia Lyakhova,4 Elena Aleshkovich,4 Anna Saribekian,2 Denis Andreev,2 Alexey Shabunin,4 Dmitry Sychev1 1Institute for Molecular and Personalized Medicine,...

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Main Authors: Rytkin E, Mirzaev K, Bure I, Akmalova K, Abdullaev S, Kachanova A, Smirnov V, Grishina E, Lyakhova N, Aleshkovich E, Saribekian A, Andreev D, Shabunin A, Sychev D
Format: Article
Language:English
Published: Dove Medical Press 2021-12-01
Series:Pharmacogenomics and Personalized Medicine
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Online Access:https://www.dovepress.com/micrornas-as-novel-biomarkers-for-p2y12--inhibitors-resistance-predict-peer-reviewed-fulltext-article-PGPM
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author Rytkin E
Mirzaev K
Bure I
Akmalova K
Abdullaev S
Kachanova A
Smirnov V
Grishina E
Lyakhova N
Aleshkovich E
Saribekian A
Andreev D
Shabunin A
Sychev D
author_facet Rytkin E
Mirzaev K
Bure I
Akmalova K
Abdullaev S
Kachanova A
Smirnov V
Grishina E
Lyakhova N
Aleshkovich E
Saribekian A
Andreev D
Shabunin A
Sychev D
author_sort Rytkin E
collection DOAJ
description Eric Rytkin,1 Karin Mirzaev,1 Irina Bure,1 Kristina Akmalova,1 Sherzod Abdullaev,1 Anastasiia Kachanova,1 Valery Smirnov,2,3 Elena Grishina,1 Natalia Lyakhova,4 Elena Aleshkovich,4 Anna Saribekian,2 Denis Andreev,2 Alexey Shabunin,4 Dmitry Sychev1 1Institute for Molecular and Personalized Medicine, Russian Medical Academy of Continuous Professional Education, Moscow, Russian Federation; 2Sechenov University, Moscow, Russian Federation; 3NRC Institute of Immunology FMBA of Russia, Moscow, Russian Federation; 4S.P. Botkin City Clinical Hospital, Moscow, Russian FederationCorrespondence: Eric Rytkin Email erytkin@gmail.comAim: 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.Keywords: biomarker, miRNA, polymorphism, acute coronary syndrome, pharmacogenomics
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spelling doaj.art-e97487e73e484319bbb5c965d97240002022-12-21T20:31:10ZengDove Medical PressPharmacogenomics and Personalized Medicine1178-70662021-12-01Volume 141575158271138MicroRNAs as Novel Biomarkers for P2Y12 – Inhibitors Resistance PredictionRytkin EMirzaev KBure IAkmalova KAbdullaev SKachanova ASmirnov VGrishina ELyakhova NAleshkovich ESaribekian AAndreev DShabunin ASychev DEric Rytkin,1 Karin Mirzaev,1 Irina Bure,1 Kristina Akmalova,1 Sherzod Abdullaev,1 Anastasiia Kachanova,1 Valery Smirnov,2,3 Elena Grishina,1 Natalia Lyakhova,4 Elena Aleshkovich,4 Anna Saribekian,2 Denis Andreev,2 Alexey Shabunin,4 Dmitry Sychev1 1Institute for Molecular and Personalized Medicine, Russian Medical Academy of Continuous Professional Education, Moscow, Russian Federation; 2Sechenov University, Moscow, Russian Federation; 3NRC Institute of Immunology FMBA of Russia, Moscow, Russian Federation; 4S.P. Botkin City Clinical Hospital, Moscow, Russian FederationCorrespondence: Eric Rytkin Email erytkin@gmail.comAim: 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.Keywords: biomarker, miRNA, polymorphism, acute coronary syndrome, pharmacogenomicshttps://www.dovepress.com/micrornas-as-novel-biomarkers-for-p2y12--inhibitors-resistance-predict-peer-reviewed-fulltext-article-PGPMbiomarkermirnapolymorphismacute coronary syndromepharmacogenomics
spellingShingle Rytkin E
Mirzaev K
Bure I
Akmalova K
Abdullaev S
Kachanova A
Smirnov V
Grishina E
Lyakhova N
Aleshkovich E
Saribekian A
Andreev D
Shabunin A
Sychev D
MicroRNAs as Novel Biomarkers for P2Y12 – Inhibitors Resistance Prediction
Pharmacogenomics and Personalized Medicine
biomarker
mirna
polymorphism
acute coronary syndrome
pharmacogenomics
title MicroRNAs as Novel Biomarkers for P2Y12 – Inhibitors Resistance Prediction
title_full MicroRNAs as Novel Biomarkers for P2Y12 – Inhibitors Resistance Prediction
title_fullStr MicroRNAs as Novel Biomarkers for P2Y12 – Inhibitors Resistance Prediction
title_full_unstemmed MicroRNAs as Novel Biomarkers for P2Y12 – Inhibitors Resistance Prediction
title_short MicroRNAs as Novel Biomarkers for P2Y12 – Inhibitors Resistance Prediction
title_sort micrornas as novel biomarkers for p2y12 ndash inhibitors resistance prediction
topic biomarker
mirna
polymorphism
acute coronary syndrome
pharmacogenomics
url https://www.dovepress.com/micrornas-as-novel-biomarkers-for-p2y12--inhibitors-resistance-predict-peer-reviewed-fulltext-article-PGPM
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