Cargando…
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...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9944402/ https://www.ncbi.nlm.nih.gov/pubmed/36843628 http://dx.doi.org/10.3389/fcvm.2022.1027892 |
_version_ | 1784891907516661760 |
---|---|
author | Giantini, Astuti Timan, Ina S. Dharma, Rahajuningsih Sukmawan, Renan Setiabudy, Rianto Alwi, Idrus Harahap, Alida R. Listiyaningsih, Erlin Partakusuma, Lia G. Tansir, Arif R. Sahar, Windy Hidayat, Rakhmad |
author_facet | Giantini, Astuti Timan, Ina S. Dharma, Rahajuningsih Sukmawan, Renan Setiabudy, Rianto Alwi, Idrus Harahap, Alida R. Listiyaningsih, Erlin Partakusuma, Lia G. Tansir, Arif R. Sahar, Windy Hidayat, Rakhmad |
author_sort | Giantini, Astuti |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-9944402 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-99444022023-02-23 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 Giantini, Astuti Timan, Ina S. Dharma, Rahajuningsih Sukmawan, Renan Setiabudy, Rianto Alwi, Idrus Harahap, Alida R. Listiyaningsih, Erlin Partakusuma, Lia G. Tansir, Arif R. Sahar, Windy Hidayat, Rakhmad Front Cardiovasc Med Cardiovascular Medicine 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. Frontiers Media S.A. 2023-02-08 /pmc/articles/PMC9944402/ /pubmed/36843628 http://dx.doi.org/10.3389/fcvm.2022.1027892 Text en Copyright © 2023 Giantini, Timan, Dharma, Sukmawan, Setiabudy, Alwi, Harahap, Listiyaningsih, Partakusuma, Tansir, Sahar and Hidayat. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cardiovascular Medicine Giantini, Astuti Timan, Ina S. Dharma, Rahajuningsih Sukmawan, Renan Setiabudy, Rianto Alwi, Idrus Harahap, Alida R. Listiyaningsih, Erlin Partakusuma, Lia G. Tansir, Arif R. Sahar, Windy Hidayat, Rakhmad 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 | 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 | Cardiovascular Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9944402/ https://www.ncbi.nlm.nih.gov/pubmed/36843628 http://dx.doi.org/10.3389/fcvm.2022.1027892 |
work_keys_str_mv | AT giantiniastuti theroleofclopidogrelresistancerelatedgeneticandepigeneticfactorsinmajoradversecardiovasculareventsamongpatientswithacutecoronarysyndromeafterpercutaneouscoronaryintervention AT timaninas theroleofclopidogrelresistancerelatedgeneticandepigeneticfactorsinmajoradversecardiovasculareventsamongpatientswithacutecoronarysyndromeafterpercutaneouscoronaryintervention AT dharmarahajuningsih theroleofclopidogrelresistancerelatedgeneticandepigeneticfactorsinmajoradversecardiovasculareventsamongpatientswithacutecoronarysyndromeafterpercutaneouscoronaryintervention AT sukmawanrenan theroleofclopidogrelresistancerelatedgeneticandepigeneticfactorsinmajoradversecardiovasculareventsamongpatientswithacutecoronarysyndromeafterpercutaneouscoronaryintervention AT setiabudyrianto theroleofclopidogrelresistancerelatedgeneticandepigeneticfactorsinmajoradversecardiovasculareventsamongpatientswithacutecoronarysyndromeafterpercutaneouscoronaryintervention AT alwiidrus theroleofclopidogrelresistancerelatedgeneticandepigeneticfactorsinmajoradversecardiovasculareventsamongpatientswithacutecoronarysyndromeafterpercutaneouscoronaryintervention AT harahapalidar theroleofclopidogrelresistancerelatedgeneticandepigeneticfactorsinmajoradversecardiovasculareventsamongpatientswithacutecoronarysyndromeafterpercutaneouscoronaryintervention AT listiyaningsiherlin theroleofclopidogrelresistancerelatedgeneticandepigeneticfactorsinmajoradversecardiovasculareventsamongpatientswithacutecoronarysyndromeafterpercutaneouscoronaryintervention AT partakusumaliag theroleofclopidogrelresistancerelatedgeneticandepigeneticfactorsinmajoradversecardiovasculareventsamongpatientswithacutecoronarysyndromeafterpercutaneouscoronaryintervention AT tansirarifr theroleofclopidogrelresistancerelatedgeneticandepigeneticfactorsinmajoradversecardiovasculareventsamongpatientswithacutecoronarysyndromeafterpercutaneouscoronaryintervention AT saharwindy theroleofclopidogrelresistancerelatedgeneticandepigeneticfactorsinmajoradversecardiovasculareventsamongpatientswithacutecoronarysyndromeafterpercutaneouscoronaryintervention AT hidayatrakhmad theroleofclopidogrelresistancerelatedgeneticandepigeneticfactorsinmajoradversecardiovasculareventsamongpatientswithacutecoronarysyndromeafterpercutaneouscoronaryintervention AT giantiniastuti roleofclopidogrelresistancerelatedgeneticandepigeneticfactorsinmajoradversecardiovasculareventsamongpatientswithacutecoronarysyndromeafterpercutaneouscoronaryintervention AT timaninas roleofclopidogrelresistancerelatedgeneticandepigeneticfactorsinmajoradversecardiovasculareventsamongpatientswithacutecoronarysyndromeafterpercutaneouscoronaryintervention AT dharmarahajuningsih roleofclopidogrelresistancerelatedgeneticandepigeneticfactorsinmajoradversecardiovasculareventsamongpatientswithacutecoronarysyndromeafterpercutaneouscoronaryintervention AT sukmawanrenan roleofclopidogrelresistancerelatedgeneticandepigeneticfactorsinmajoradversecardiovasculareventsamongpatientswithacutecoronarysyndromeafterpercutaneouscoronaryintervention AT setiabudyrianto roleofclopidogrelresistancerelatedgeneticandepigeneticfactorsinmajoradversecardiovasculareventsamongpatientswithacutecoronarysyndromeafterpercutaneouscoronaryintervention AT alwiidrus roleofclopidogrelresistancerelatedgeneticandepigeneticfactorsinmajoradversecardiovasculareventsamongpatientswithacutecoronarysyndromeafterpercutaneouscoronaryintervention AT harahapalidar roleofclopidogrelresistancerelatedgeneticandepigeneticfactorsinmajoradversecardiovasculareventsamongpatientswithacutecoronarysyndromeafterpercutaneouscoronaryintervention AT listiyaningsiherlin roleofclopidogrelresistancerelatedgeneticandepigeneticfactorsinmajoradversecardiovasculareventsamongpatientswithacutecoronarysyndromeafterpercutaneouscoronaryintervention AT partakusumaliag roleofclopidogrelresistancerelatedgeneticandepigeneticfactorsinmajoradversecardiovasculareventsamongpatientswithacutecoronarysyndromeafterpercutaneouscoronaryintervention AT tansirarifr roleofclopidogrelresistancerelatedgeneticandepigeneticfactorsinmajoradversecardiovasculareventsamongpatientswithacutecoronarysyndromeafterpercutaneouscoronaryintervention AT saharwindy roleofclopidogrelresistancerelatedgeneticandepigeneticfactorsinmajoradversecardiovasculareventsamongpatientswithacutecoronarysyndromeafterpercutaneouscoronaryintervention AT hidayatrakhmad roleofclopidogrelresistancerelatedgeneticandepigeneticfactorsinmajoradversecardiovasculareventsamongpatientswithacutecoronarysyndromeafterpercutaneouscoronaryintervention |