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The DNAm levels of CREB5 (cg11301281) were associated with clopidogrel resistance
Jiyi Li1, Jin Yang2, Qinglin Yu3
1Department of Cardiology, Yuyao People's Hospital of Zhejiang Province, Ningbo, China.
Insights
Lower DNA methylation of CREB5 (cg01534253) is linked to clopidogrel resistance (CR) in acute coronary syndrome (ACS) patients with elevated blood glucose. This finding may improve personalized antiplatelet therapy for ACS patients.
Area of Science:
- Cardiovascular Medicine
- Pharmacogenomics
- Epigenetics
Background:
- Clopidogrel resistance (CR) contributes to cardiovascular events due to variable platelet inhibition.
- Understanding the mechanisms behind CR is crucial for optimizing antiplatelet therapy.
Purpose of the Study:
- To investigate the role of CREB5 DNA methylation (cg01534253) in clopidogrel resistance (CR) among acute coronary syndrome (ACS) patients.
- To explore the relationship between CREB5 methylation, gene expression, and clinical factors in CR.
Main Methods:
- Analyzed 72 ACS patients (36 CR, 36 non-CR) using the VerifyNow P2Y12 assay for platelet reactivity.
- Assessed DNA methylation at cg01534253 via bisulfite pyrosequencing and CREB5 mRNA expression using quantitative real-time PCR.
- Utilized logistic regression to identify clinical variables interacting with CREB5 methylation in CR.
Main Results:
- Lower cg01534253 methylation correlated with poorer clopidogrel response in patients with HbA1c ≥6.5% or GLU ≥7 mmol/L.
- Increased CREB5 mRNA expression was observed in CR patients with GLU ≥7 mmol/L.
- Albumin and uric acid levels were associated with the incidence of CR.
Conclusions:
- Findings suggest a novel epigenetic mechanism contributing to clopidogrel resistance.
- This research may facilitate individualized antiplatelet strategies for ACS patients.
Purpose:
Clopidogrel resistance (CR) is mostly caused by interindividual variability of the platelet inhibition of clopidogrel, which may induce cardiovascular events. The aim of this research was to evaluate whether DNAm levels of CREB5 (cg01534253) are involved in CR among acute coronary syndrome (ACS) patients treated with clopidogrel.
Methods:
72 patients(36 CR and 36 non-CR) who underwent ACS were included in this study. The VerifyNow P2Y12 assay was selected to evaluate residual platelet reactivity, and bisulfite pyrosequencing methods was used to examine DNA methylation levels on cg01534253. Secondly, CREB5 mRNA expression was analyzed via quantitative real-time PCR. Last, we employed logistic regression to test the interaction between genetic factors of CREB5 methylation and multiple clinical variables in CR patients.
Results:
Subunit analysis indicated that for patients whose HbA1c levels were ≥6.5% or whose GLU levels were ≥7 mmol/L, lower methylation of cg01534253 indicated a poorer clopidogrel response. In addition, CREB5 mRNA expression was increased in CR patients with GLU levels ≥7 mmol/L. Moreover, regression analysis indicated that the values of albumin and uric acid were correlated with the incidence of CR.
Conclusions:
Our findings were likely to provide fresh understanding for the new mechanism of platelet inhibition failure and promote individualized antiplatelet therapy.
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