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,...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: 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
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2021
Materias:
Acceso en línea:https://doaj.org/article/e97487e73e484319bbb5c965d9724000
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:e97487e73e484319bbb5c965d9724000
record_format dspace
spelling oai:doaj.org-article:e97487e73e484319bbb5c965d97240002021-12-02T19:17:36ZMicroRNAs as Novel Biomarkers for P2Y12 – Inhibitors Resistance Prediction1178-7066https://doaj.org/article/e97487e73e484319bbb5c965d97240002021-12-01T00:00:00Zhttps://www.dovepress.com/micrornas-as-novel-biomarkers-for-p2y12--inhibitors-resistance-predict-peer-reviewed-fulltext-article-PGPMhttps://doaj.org/toc/1178-7066Eric 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, pharmacogenomicsRytkin EMirzaev KBure IAkmalova KAbdullaev SKachanova ASmirnov VGrishina ELyakhova NAleshkovich ESaribekian AAndreev DShabunin ASychev DDove Medical Pressarticlebiomarkermirnapolymorphismacute coronary syndromepharmacogenomicsTherapeutics. PharmacologyRM1-950ENPharmacogenomics and Personalized Medicine, Vol Volume 14, Pp 1575-1582 (2021)
institution DOAJ
collection DOAJ
language EN
topic biomarker
mirna
polymorphism
acute coronary syndrome
pharmacogenomics
Therapeutics. Pharmacology
RM1-950
spellingShingle biomarker
mirna
polymorphism
acute coronary syndrome
pharmacogenomics
Therapeutics. Pharmacology
RM1-950
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
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
format article
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
title MicroRNAs as Novel Biomarkers for P2Y12 – Inhibitors Resistance Prediction
title_short 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_sort micrornas as novel biomarkers for p2y12 – inhibitors resistance prediction
publisher Dove Medical Press
publishDate 2021
url https://doaj.org/article/e97487e73e484319bbb5c965d9724000
work_keys_str_mv AT rytkine micrornasasnovelbiomarkersforp2y12ndashinhibitorsresistanceprediction
AT mirzaevk micrornasasnovelbiomarkersforp2y12ndashinhibitorsresistanceprediction
AT burei micrornasasnovelbiomarkersforp2y12ndashinhibitorsresistanceprediction
AT akmalovak micrornasasnovelbiomarkersforp2y12ndashinhibitorsresistanceprediction
AT abdullaevs micrornasasnovelbiomarkersforp2y12ndashinhibitorsresistanceprediction
AT kachanovaa micrornasasnovelbiomarkersforp2y12ndashinhibitorsresistanceprediction
AT smirnovv micrornasasnovelbiomarkersforp2y12ndashinhibitorsresistanceprediction
AT grishinae micrornasasnovelbiomarkersforp2y12ndashinhibitorsresistanceprediction
AT lyakhovan micrornasasnovelbiomarkersforp2y12ndashinhibitorsresistanceprediction
AT aleshkoviche micrornasasnovelbiomarkersforp2y12ndashinhibitorsresistanceprediction
AT saribekiana micrornasasnovelbiomarkersforp2y12ndashinhibitorsresistanceprediction
AT andreevd micrornasasnovelbiomarkersforp2y12ndashinhibitorsresistanceprediction
AT shabunina micrornasasnovelbiomarkersforp2y12ndashinhibitorsresistanceprediction
AT sychevd micrornasasnovelbiomarkersforp2y12ndashinhibitorsresistanceprediction
_version_ 1718376887116365824