Pharmacogenetics in treatment of anthracycline-induced cardiotoxicity in women without prior cardiovascular diseases

Aim. To evaluate the role of polymorphisms in adrenoceptor beta 1 (ADRB1) (Arg389Gly, rs1801253) and angiotensin-converting enzyme (ACE) (I/D, rs4343) genes in assessing the effectiveness of β-blocker (carvedilol) and ACE inhibitor (enalapril) therapy in women with anthracycline-induced cardiotoxici...

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Main Authors: E. V. Grakova, K. V. Kopeva, S. N. Shilov, E. N. Berezikova, A. A. Popova, M. N. Neupokoeva, E. T. Ratushnyak, V. V. Kalyuzhin, A. T. Teplyakov
Format: Article
Language:English
Published: Siberian State Medical University (Tomsk) 2023-01-01
Series:Бюллетень сибирской медицины
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Online Access:https://bulletin.ssmu.ru/jour/article/view/5020
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author E. V. Grakova
K. V. Kopeva
S. N. Shilov
E. N. Berezikova
A. A. Popova
M. N. Neupokoeva
E. T. Ratushnyak
V. V. Kalyuzhin
A. T. Teplyakov
author_facet E. V. Grakova
K. V. Kopeva
S. N. Shilov
E. N. Berezikova
A. A. Popova
M. N. Neupokoeva
E. T. Ratushnyak
V. V. Kalyuzhin
A. T. Teplyakov
author_sort E. V. Grakova
collection DOAJ
description Aim. To evaluate the role of polymorphisms in adrenoceptor beta 1 (ADRB1) (Arg389Gly, rs1801253) and angiotensin-converting enzyme (ACE) (I/D, rs4343) genes in assessing the effectiveness of β-blocker (carvedilol) and ACE inhibitor (enalapril) therapy in women with anthracycline-induced cardiotoxicity (AIC) without prior cardiovascular diseases (CVD) during 12-month follow-up.Materials and methods. A total of 82 women (average age 45.0 (42.0; 50.0) years) with AIC and without prior CVD were included in the study. Echocardiography was performed and serum levels of NT-proBNP were determined at baseline and at 12 months after the enrollment. Gene polymorphisms in ADRB1 and ACE genes were evaluated by polymerase chain reaction at baseline.Results. Carriers of the G/G genotype in the ADRB1 gene and G/G genotype in the ACE (I/D, rs4343) gene showed a significant increase in left ventricular ejection fraction (LVEF), a decrease in the size of the left ventricle (LV) and left atrium (LA), and a fall in the NT-proBNP level. Carriers of other genotypes had further progression of AIC which was manifested through a decrease in LVEF and an increase in the size of LV and LA.Conclusion. Evaluation of gene polymorphisms in ADRB1 (Arg389Gly, rs1801253) and ACE (I/D, rs4343) genes may be recommended before treatment initiation for AIC in women without prior CVD to determine who will benefit from carvedilol and enalapril therapy, as well as to identify a priority group of patients for personalized intensification and optimization of treatment for decreasing development of adverse cardiovascular events.
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spelling doaj-art-d716a486ddc14e388bcef4acedb284432025-08-20T03:37:46ZengSiberian State Medical University (Tomsk)Бюллетень сибирской медицины1682-03631819-36842023-01-01214445310.20538/1682-0363-2022-4-44-532940Pharmacogenetics in treatment of anthracycline-induced cardiotoxicity in women without prior cardiovascular diseasesE. V. Grakova0K. V. Kopeva1S. N. Shilov2E. N. Berezikova3A. A. Popova4M. N. Neupokoeva5E. T. Ratushnyak6V. V. Kalyuzhin7A. T. Teplyakov8Cardiology Research Institute, Tomsk National Research Medical Center (NRMC), Russian Academy of SciencesCardiology Research Institute, Tomsk National Research Medical Center (NRMC), Russian Academy of SciencesNovosibirsk State Medical University (NSMU)Novosibirsk State Medical University (NSMU)Novosibirsk State Medical University (NSMU)Novosibirsk State Medical University (NSMU)Novosibirsk State Medical University (NSMU)Siberian State Medical University (SSMU)Cardiology Research Institute, Tomsk National Research Medical Center (NRMC), Russian Academy of SciencesAim. To evaluate the role of polymorphisms in adrenoceptor beta 1 (ADRB1) (Arg389Gly, rs1801253) and angiotensin-converting enzyme (ACE) (I/D, rs4343) genes in assessing the effectiveness of β-blocker (carvedilol) and ACE inhibitor (enalapril) therapy in women with anthracycline-induced cardiotoxicity (AIC) without prior cardiovascular diseases (CVD) during 12-month follow-up.Materials and methods. A total of 82 women (average age 45.0 (42.0; 50.0) years) with AIC and without prior CVD were included in the study. Echocardiography was performed and serum levels of NT-proBNP were determined at baseline and at 12 months after the enrollment. Gene polymorphisms in ADRB1 and ACE genes were evaluated by polymerase chain reaction at baseline.Results. Carriers of the G/G genotype in the ADRB1 gene and G/G genotype in the ACE (I/D, rs4343) gene showed a significant increase in left ventricular ejection fraction (LVEF), a decrease in the size of the left ventricle (LV) and left atrium (LA), and a fall in the NT-proBNP level. Carriers of other genotypes had further progression of AIC which was manifested through a decrease in LVEF and an increase in the size of LV and LA.Conclusion. Evaluation of gene polymorphisms in ADRB1 (Arg389Gly, rs1801253) and ACE (I/D, rs4343) genes may be recommended before treatment initiation for AIC in women without prior CVD to determine who will benefit from carvedilol and enalapril therapy, as well as to identify a priority group of patients for personalized intensification and optimization of treatment for decreasing development of adverse cardiovascular events.https://bulletin.ssmu.ru/jour/article/view/5020anthracycline-induced cardiotoxicityheart failuregene polymorphismsβ-blockerangiotensin-converting enzyme inhibitor
spellingShingle E. V. Grakova
K. V. Kopeva
S. N. Shilov
E. N. Berezikova
A. A. Popova
M. N. Neupokoeva
E. T. Ratushnyak
V. V. Kalyuzhin
A. T. Teplyakov
Pharmacogenetics in treatment of anthracycline-induced cardiotoxicity in women without prior cardiovascular diseases
Бюллетень сибирской медицины
anthracycline-induced cardiotoxicity
heart failure
gene polymorphisms
β-blocker
angiotensin-converting enzyme inhibitor
title Pharmacogenetics in treatment of anthracycline-induced cardiotoxicity in women without prior cardiovascular diseases
title_full Pharmacogenetics in treatment of anthracycline-induced cardiotoxicity in women without prior cardiovascular diseases
title_fullStr Pharmacogenetics in treatment of anthracycline-induced cardiotoxicity in women without prior cardiovascular diseases
title_full_unstemmed Pharmacogenetics in treatment of anthracycline-induced cardiotoxicity in women without prior cardiovascular diseases
title_short Pharmacogenetics in treatment of anthracycline-induced cardiotoxicity in women without prior cardiovascular diseases
title_sort pharmacogenetics in treatment of anthracycline induced cardiotoxicity in women without prior cardiovascular diseases
topic anthracycline-induced cardiotoxicity
heart failure
gene polymorphisms
β-blocker
angiotensin-converting enzyme inhibitor
url https://bulletin.ssmu.ru/jour/article/view/5020
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