pmedpharmФармация и фармакологияPharmacy & Pharmacology2307-92662413-2241Pyatigorsk Medical and Pharmaceutical Institute - branch of Volgograd State Medical Univer10.19163/2307-9266-2026-14-3-218-235pmedpharm-1893Research ArticleОБЗОРЫREVIEWСистематический обзор влияния уровня метилирования ДНК на эффективность антагонистов рецепторов P2Y12Systematic review of the influence of DNA methylation level on the efficacy of P2Y12 receptor antagonistshttps://orcid.org/0009-0001-2744-2752ТучковаС. Н.TuchkovaS. N.

младший научный сотрудник отдела предиктивных и прогностических биомаркеров НИИ молекулярной и персонализированной медицины, ФГБОУ ДПО РМАНПО Минздрава России; младший научный сотрудник отдела фармакогенетики и персонализированной терапии Центра геномных исследований мирового уровня «Центр предиктивной генетики, фармакогенетики и персонализированной терапии», ФГБНУ РНЦХ им. акад. Б.В. Петровского. 

1. Россия, 125993, г. Москва, ул. Баррикадная, д. 2/1, стр. 1.

2. Россия, 119991, г. Москва, Абрикосовский пер., д. 2. 

 

Junior Researcher at the Department of Predictive and Prognostic Biomarkers at the Research Institute of Molecular and Personalized Medicine, Russian Medical Academy of Continuous Professional Education; Junior Researcher at the Department of Pharmacogenetics and Personalized Therapy of the World-class Center for Genomic Research "Center for Predictive Genetics, Pharmacogenetics and Personalized Therapy", Russian Scientific Center for Surgery named after Academician B.V. Petrovsky.

1. 2/1 Barrikadnaya Str., Bldg. 1, Moscow, Russia, 125993.

2. 2 Abrikosovsky Ln., Moscow, Russia, 119991. 

svetlana.tuch1998@gmail.comhttps://orcid.org/0000-0001-9001-1499АбдуллаевШ. П.AbdullaevSh. P.

кандидат биологических наук, старший научный сотрудник, заведующий отделом предиктивных и прогностических биомаркеров НИИ молекулярной и персонализированной медицины, ФГБОУ ДПО РМАНПО Минздрава России; старший научный сотрудник отдела фармакогенетики и персонализированной терапии Центра геномных исследований мирового уровня «Центр предиктивной генетики, фармакогенетики и персонализированной терапии», ФГБНУ РНЦХ им. акад. Б.В. Петровского.

1. Россия, 125993, г. Москва, ул. Баррикадная, д. 2/1, стр. 1.

2. Россия, 119991, г. Москва, Абрикосовский пер., д. 2. 

 

 

Candidate of Sciences (Biology), Senior Researcher, Head of the Department of Predictive and Prognostic Biomarkers at the Research Institute of Molecular and Personalized Medicine, Russian Medical Academy of Continuous Professional Education; Senior Researcher of the Department of Pharmacogenetics and Personalized Therapy at the World-class Center for Genomic Research "Center for Predictive Genetics, Pharmacogenetics and Personalized Therapy", Russian Scientific Center for Surgery named after Academician B.V. Petrovsky. 

1. 2/1 Barrikadnaya Str., Bldg. 1, Moscow, Russia, 125993.

2. 2 Abrikosovsky Ln., Moscow, Russia, 119991. 

abdullaevsp@gmail.comhttps://orcid.org/0000-0003-3278-5941ДенисенкоН. П.DenisenkoN. P.

кандидат медицинских наук, доцент, доцент кафедры клинической фармакологии и терапии имени академика Б.Е. Вотчала, ФГБОУ ДПО РМАНПО Минздрава России; старший научный сотрудник Центра геномных исследований мирового уровня «Центр предиктивной генетики, фармакогенетики и персонализированной терапии», ФГБНУ РНЦХ им. акад. Б.В. Петровского.

 

1. Россия, 125993, г. Москва, ул. Баррикадная, д. 2/1, стр. 1.

2. Россия, 119991, г. Москва, Абрикосовский пер., д. 2. 

Candidate of Sciences (Medicine), Assistant Professor of the Department of Clinical Pharmacology and Therapy named after Academician B.E. Votchal, Russian Medical Academy of Continuous Professional Education; Senior Researcher at the World-class Center for Genomic Research "Center for Predictive Genetics, Pharmacogenetics and Personalized Therapy", Russian Scientific Center for Surgery named after Academician B.V. Petrovsky.

1. 2/1 Barrikadnaya Str., Bldg. 1, Moscow, Russia, 125993.

2. 2 Abrikosovsky Ln., Moscow, Russia, 119991. 

natalypilipenko3990@gmail.comhttps://orcid.org/0000-0002-9307-4994МирзаевК. Б.MirzaevK. B.

доктор медицинских наук, доцент, профессор кафедры клинической фармакологии и терапии им. академика Б.Е. Вотчала, ФГБОУ ДПО РМАНПО Минздрава России; заместитель руководителя Центра геномных исследований мирового уровня «Центр предиктивной генетики, фармакогенетики и персонализированной терапии», ФГБНУ РНЦХ им. акад. Б.В. Петровского.

 

1. Россия, 125993, г. Москва, ул. Баррикадная, д. 2/1, стр. 1.

2. Россия, 119991, г. Москва, Абрикосовский пер., д. 2. 

Doctor of Sciences (Medicine), Assistant Professor, Professor of the Department of Clinical Pharmacology and Therapy. Academician B.E. Votchal, Russian Medical Academy of Continuous Professional Education; Deputy Head of the World-class Center for Genomic Research "Center for Predictive Genetics, Pharmacogenetics and Personalized Therapy", Russian Scientific Center for Surgery named after Academician B.V. Petrovsky. 

1. 2/1 Barrikadnaya Str., Bldg. 1, Moscow, Russia, 125993.

2. 2 Abrikosovsky Ln., Moscow, Russia, 119991. 

karin05doc@yandex.ruhttps://orcid.org/0000-0002-4496-3680СычевД. А.SychevD. A.

доктор медицинских наук, профессор, заведующий кафедрой клинической фармакологии и терапии им. академика Б.Е. Вотчала, ФГБОУ ДПО РМАНПО Минздрава России; руководитель Центра геномных исследований мирового уровня «Центр предиктивной генетики, фармакогенетики и персонализированной терапии», ФГБНУ РНЦХ им. акад. Б.В. Петровского; академик РАН. 

 

1. Россия, 125993, г. Москва, ул. Баррикадная, д. 2/1, стр. 1.

2. Россия, 119991, г. Москва, Абрикосовский пер., д. 2. 

Doctor of Sciences (Medicine), Professor, Head of the Department of Clinical Pharmacology and Therapy. Academician B.E. Votchal, Russian Medical Academy of Continuous Professional Education; Head of the World-class Center for Genomic Research "Center for Predictive Genetics, Pharmacogenetics and Personalized Therapy", Russian Scientific Center for Surgery named after Academician B.V. Petrovsky; Academician of the Russian Academy of Sciences. 

1. 2/1 Barrikadnaya Str., Bldg. 1, Moscow, Russia, 125993.

2. 2 Abrikosovsky Ln., Moscow, Russia, 119991. 

dimasychev@mail.ru1. Федеральное государственное бюджетное образовательное учреждение дополнительного профессионального образования «Российская медицинская академия непрерывного профессионального образования» Министерства здравоохранения Российской Федерации. 2. Федеральное государственное бюджетное научное учреждение «Российский научный центр хирургии имени академика Б.В. Петровского».Россия1. Russian Medical Academy of Continuous Professional Education. 2. Russian Scientific Center for Surgery named after Academician B.V. Petrovsky.Russian Federation202618062026143218235Copyright © Тучкова С.Н., Абдуллаев Ш.П., Денисенко Н.П., Мирзаев К.Б., Сычев Д.А., 20262026Тучкова С.Н., Абдуллаев Ш.П., Денисенко Н.П., Мирзаев К.Б., Сычев Д.А.Tuchkova S.N., Abdullaev S.P., Denisenko N.P., Mirzaev K.B., Sychev D.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmpharm.ru/jour/article/view/1893

Назначение антиагрегантов является важной частью терапии острого коронарного синдрома и других сердечно-сосудистых заболеваний. От эффективности данных препаратов зависит риск рецидива ишемических событий.

Цель

Цель. Обобщение и анализ современных научных данных о влиянии уровня метилирования ДНК на эффективность терапии антагонистами рецепторов P2Y12.

Материалы и методы

Материалы и методы. Проведён поиск научных статей в базе данных PubMed. В систематический обзор включены исследования, отражающие связь между метилированием ДНК и эффективностью клопидогрела. Исследований, посвящённых влиянию метилирования ДНК на эффективность антагонистов P2Y12-рецепторов нового поколения не найдено.

Результаты

Результаты. В обзор вошли 17 исследований с общим числом участников 3441 человек. Проанализировано влияние метилирования 20 генов: ABCB1, ABCC3, ALOX12, ALOX15, BTG2, CD80, COX1, COX2, CREB5, CYP2C19, GCK, GNAQ, P2Y12, PEAR1, PER3, PON1, PRG2, TRAF3, TBXAS1, VTRNA2-1. В 9 исследованиях выявлена связь между уровнем метилирования и риском развития резистентности к клопидогрелу, в 5 исследованиях обнаружена связь между метилированием ДНК и риском развития таких нежелательных реакций, как кровотечения или повторные ишемические события. Обнаружено, что у пациентов, имеющих гипометилирование промотора гена CYP2C19 риск возникновения резистентности к клопидогрелу выше (уровень метилирования в группе с резистентностью к клопидогрелу — 8,8±22,7%, в контрольной — 76,7±32,9%, p=0,03). Гиперметилирование промотора P2Y12 также повышает риск возникновения резистентности к препарату (0,48±0,14 против 0,86±0,13%, p <0,001).

Заключение

Заключение. Метилирование ДНК генов, продукты которых участвуют в метаболизме клопидогрела, агрегации тромбоцитов и других процессах, влияет на эффективность клопидогрела. Уровень метилирования ДНК является перспективным биомаркёром. Необходимы дополнительные исследования, подтверждающие имеющиеся научные данные, и исследования, направленные на изучение связи между уровнем метилирования и эффективностью антагонистов рецепторов P2Y12 нового поколения.

The prescription of antiplatelet agents is an important part of the therapy for acute coronary syndrome and other cardiovascular diseases. The risk of recurrent ischemic events depends on the efficacy of these drugs.

The aim

The aim. To summarize and analyze current scientific data on the influence of DNA methylation level on the efficacy of therapy with P2Y12 receptor antagonists.

Materials and methods

Materials and methods. A search for scientific articles was conducted in the PubMed database. The systematic review included studies reflecting the relationship between DNA methylation and the efficacy of clopidogrel. No studies were found concerning the influence of DNA methylation on the efficacy of next-generation P2Y12 receptor antagonists.

Results

Results. The review included 17 studies with a total of 3 441 participants. The influence of methylation of 20 genes was analyzed: ABCB1, ABCC3, ALOX12, ALOX15, BTG2, CD80, COX1, COX2, CREB5, CYP2C19, GCK, GNAQ, P2Y12, PEAR1, PER3, PON1, PRG2, TRAF3, TBXAS1, VTRNA2-1. In 9 studies, a bond was found between methylation levels and the risk of developing clopidogrel resistance. In 5 studies, a bond was found between DNA methylation and the risk of developing adverse reactions such as bleeding or recurrent ischemic events. It was found that patients with hypomethylation of the CYP2C19 gene promoter have a higher risk of developing clopidogrel resistance (methylation level in the clopidogrel resistance group is 8.8 ± 22.7 %, in the control group — 76.7 ± 32.9 %, p = 0.03). Hypermethylation of the P2Y12 promoter also increases the risk of developing resistance to the drug (0.48 ± 0.14 % vs. 0.86 ± 0.13 %, p < 0.001).

Conclusion

Conclusion. The products of DNA methylation of genes are involved in clopidogrel metabolism, platelet aggregation, and other processes affects clopidogrel efficacy. DNA methylation level is a promising biomarker. Additional confirmatory studies are needed, as well as studies on the relationship between the methylation level and the efficacy of next-generation P2Y12 receptor antagonists.

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The authors declare that there are no conflicts of interest present.