The role of clopidogrel resistance-related genetic and epigenetic factors in major adverse cardiovascular events among patients with acute coronary syndrome after percutaneous coronary intervention
Despite patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) and receiving clopidogrel therapy, some patients still experience major adverse cardiovascular events (MACEs). Clopidogrel resistance, which may be regulated by genetic and epigenetic factors, may...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2022.1027892/full |
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| author | Astuti Giantini Astuti Giantini Ina S. Timan Rahajuningsih Dharma Renan Sukmawan Rianto Setiabudy Idrus Alwi Alida R. Harahap Erlin Listiyaningsih Lia G. Partakusuma Arif R. Tansir Windy Sahar Rakhmad Hidayat Rakhmad Hidayat |
| author_facet | Astuti Giantini Astuti Giantini Ina S. Timan Rahajuningsih Dharma Renan Sukmawan Rianto Setiabudy Idrus Alwi Alida R. Harahap Erlin Listiyaningsih Lia G. Partakusuma Arif R. Tansir Windy Sahar Rakhmad Hidayat Rakhmad Hidayat |
| author_sort | Astuti Giantini |
| collection | DOAJ |
| description | Despite patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) and receiving clopidogrel therapy, some patients still experience major adverse cardiovascular events (MACEs). Clopidogrel resistance, which may be regulated by genetic and epigenetic factors, may play a role in MACEs. This study aimed to determine the association between genetic (CYP2C19 and P2Y12 polymorphisms) and epigenetic (DNA methylation of CYP2C19 and P2Y12 and miRNA-26a expression) factors and their effects on MACEs among post-PCI patients. Post-PCI patients who received a standard dosage of clopidogrel at Harapan Kita Hospital between September 2018 and June 2020 were included in this study. MACEs were observed in patients within 1 year after PCI. Platelet aggregation was assessed using light transmission aggregometry (LTA). DNA methylation of CYP2C19 and P2Y12 was assessed using the bisulfite conversion method. CYP2C19 and P2Y12 polymorphisms and miRNA-26a expression were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR). Among a total of 201 subjects, 49.8% were clopidogrel-resistant, and 14.9% experienced MACEs within 1 year after PCI (death was 7.5%). Hypomethylation of CYP2C19 (p = 0.037) and miRNA-26a upregulation (p = 0.020) were associated with clopidogrel resistance. CYP2C19*2/*3 polymorphisms (p = 0.047) were associated with MACEs in 1 year. This study demonstrated that hypomethylation of CYP2C19 and miRNA-26a upregulation increased the risk of clopidogrel resistance in post-PCI patients, but there was no correlation between clopidogrel resistance and MACEs. However, CYP2C19*2/*3 polymorphisms were the factors that predicted MACEs within 1 year. |
| first_indexed | 2024-04-10T16:42:05Z |
| format | Article |
| id | doaj.art-61b9c955bcb14552a634b64f5617959b |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-04-10T16:42:05Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-61b9c955bcb14552a634b64f5617959b2023-02-08T05:38:29ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2023-02-01910.3389/fcvm.2022.10278921027892The role of clopidogrel resistance-related genetic and epigenetic factors in major adverse cardiovascular events among patients with acute coronary syndrome after percutaneous coronary interventionAstuti Giantini0Astuti Giantini1Ina S. Timan2Rahajuningsih Dharma3Renan Sukmawan4Rianto Setiabudy5Idrus Alwi6Alida R. Harahap7Erlin Listiyaningsih8Lia G. Partakusuma9Arif R. Tansir10Windy Sahar11Rakhmad Hidayat12Rakhmad Hidayat13Clinical Pathology Department, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo National Public Hospital, Central Jakarta, IndonesiaUniversitas Indonesia Hospital, Universitas Indonesia, Depok, IndonesiaClinical Pathology Department, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo National Public Hospital, Central Jakarta, IndonesiaClinical Pathology Department, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo National Public Hospital, Central Jakarta, IndonesiaCardiology and Vascular Medicine Department, Faculty of Medicine, Universitas Indonesia, National Cardiovascular Center Harapan Kita, West Jakarta, IndonesiaPharmacology and Therapeutics Department, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo National Public Hospital, Central Jakarta, IndonesiaInternal Medicine Department, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo National Public Hospital, Central Jakarta, IndonesiaClinical Pathology Department, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo National Public Hospital, Central Jakarta, IndonesiaNational Cardiovascular Center Harapan Kita, West Jakarta, IndonesiaNational Cardiovascular Center Harapan Kita, West Jakarta, IndonesiaFaculty of Medicine, Universitas Indonesia, Central Jakarta, IndonesiaUniversitas Indonesia Hospital, Universitas Indonesia, Depok, IndonesiaUniversitas Indonesia Hospital, Universitas Indonesia, Depok, IndonesiaNeurology Department, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo National Public Hospital, Central Jakarta, IndonesiaDespite patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) and receiving clopidogrel therapy, some patients still experience major adverse cardiovascular events (MACEs). Clopidogrel resistance, which may be regulated by genetic and epigenetic factors, may play a role in MACEs. This study aimed to determine the association between genetic (CYP2C19 and P2Y12 polymorphisms) and epigenetic (DNA methylation of CYP2C19 and P2Y12 and miRNA-26a expression) factors and their effects on MACEs among post-PCI patients. Post-PCI patients who received a standard dosage of clopidogrel at Harapan Kita Hospital between September 2018 and June 2020 were included in this study. MACEs were observed in patients within 1 year after PCI. Platelet aggregation was assessed using light transmission aggregometry (LTA). DNA methylation of CYP2C19 and P2Y12 was assessed using the bisulfite conversion method. CYP2C19 and P2Y12 polymorphisms and miRNA-26a expression were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR). Among a total of 201 subjects, 49.8% were clopidogrel-resistant, and 14.9% experienced MACEs within 1 year after PCI (death was 7.5%). Hypomethylation of CYP2C19 (p = 0.037) and miRNA-26a upregulation (p = 0.020) were associated with clopidogrel resistance. CYP2C19*2/*3 polymorphisms (p = 0.047) were associated with MACEs in 1 year. This study demonstrated that hypomethylation of CYP2C19 and miRNA-26a upregulation increased the risk of clopidogrel resistance in post-PCI patients, but there was no correlation between clopidogrel resistance and MACEs. However, CYP2C19*2/*3 polymorphisms were the factors that predicted MACEs within 1 year.https://www.frontiersin.org/articles/10.3389/fcvm.2022.1027892/fullacute coronary syndromeclopidogrel resistanceepigenetic factorgenetic factormajor adverse cardiovascular events |
| spellingShingle | Astuti Giantini Astuti Giantini Ina S. Timan Rahajuningsih Dharma Renan Sukmawan Rianto Setiabudy Idrus Alwi Alida R. Harahap Erlin Listiyaningsih Lia G. Partakusuma Arif R. Tansir Windy Sahar Rakhmad Hidayat Rakhmad Hidayat The role of clopidogrel resistance-related genetic and epigenetic factors in major adverse cardiovascular events among patients with acute coronary syndrome after percutaneous coronary intervention Frontiers in Cardiovascular Medicine acute coronary syndrome clopidogrel resistance epigenetic factor genetic factor major adverse cardiovascular events |
| title | The role of clopidogrel resistance-related genetic and epigenetic factors in major adverse cardiovascular events among patients with acute coronary syndrome after percutaneous coronary intervention |
| title_full | The role of clopidogrel resistance-related genetic and epigenetic factors in major adverse cardiovascular events among patients with acute coronary syndrome after percutaneous coronary intervention |
| title_fullStr | The role of clopidogrel resistance-related genetic and epigenetic factors in major adverse cardiovascular events among patients with acute coronary syndrome after percutaneous coronary intervention |
| title_full_unstemmed | The role of clopidogrel resistance-related genetic and epigenetic factors in major adverse cardiovascular events among patients with acute coronary syndrome after percutaneous coronary intervention |
| title_short | The role of clopidogrel resistance-related genetic and epigenetic factors in major adverse cardiovascular events among patients with acute coronary syndrome after percutaneous coronary intervention |
| title_sort | role of clopidogrel resistance related genetic and epigenetic factors in major adverse cardiovascular events among patients with acute coronary syndrome after percutaneous coronary intervention |
| topic | acute coronary syndrome clopidogrel resistance epigenetic factor genetic factor major adverse cardiovascular events |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2022.1027892/full |
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