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 

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

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=9

YEAR=2023

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.1027892

DOI=10.3389/fcvm.2022.1027892

ISSN=2297-055X

ABSTRACT=<p>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 (<italic>CYP2C19</italic> and <italic>P2Y12</italic> polymorphisms) and epigenetic (DNA methylation of <italic>CYP2C19</italic> and <italic>P2Y12</italic> 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 <italic>CYP2C19</italic> and <italic>P2Y12</italic> was assessed using the bisulfite conversion method. <italic>CYP2C19</italic> and <italic>P2Y12</italic> 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 <italic>CYP2C19</italic> (<italic>p</italic> = 0.037) and miRNA-26a upregulation (<italic>p</italic> = 0.020) were associated with clopidogrel resistance. CYP2C19<sup>*</sup>2/<sup>*</sup>3 polymorphisms (<italic>p</italic> = 0.047) were associated with MACEs in 1 year. This study demonstrated that hypomethylation of <italic>CYP2C19</italic> 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<sup>*</sup>2/<sup>*</sup>3 polymorphisms were the factors that predicted MACEs within 1 year.</p>