Abstract
Background and AimsThe failure of therapeutic response to clopidogrel in platelet inhibition, which is called clopidogrel resistance (CR), is more likely to cause cardiovascular events. We aimed to study the contribution of promoter DNA methylation of paraoxonase 1 (PON1) to the risk of clopidogrel poor response.MethodsThrough VerifyNow P2Y12 assay, patient’ platelet functions were measured. Among 57 non‐CR and 49 CR patients, the levels of DNA methylation in four CpG dinucleotides on the PON1 promoter were tested using bisulfite pyrosequencing technology. Besides, the relative expression of PON1 mRNA was analyzed by quantitative real‐time PCR. Logistic regression was applied to investigate the interaction of PON1 methylation and clinical factors in CR.ResultsIn the subgroup with dyslipidemia, we discovered that higher CpG4 levels of the PON1 promoter indicated a poorer clopidogrel response (cases versus controls (%): 51.500 ± 14.742 vs 43.308 ± 10.891, P = 0.036), and the PON1 mRNA expression was reduced in CR patients. Additionally, the logistic regression indicated that higher level of albumin and the index of ALT were related to a lower risk of CR, and the index of AST as well as the quantity of stent may be positively associated with CR.ConclusionsThe DNA methylation of CpG4 in the PON1 promoter would lead to a low expression of PON1 mRNA, which might induce clopidogrel resistance in the patients with dyslipidemia, and the number of stents might be a risk for CR.
Highlights
Atherosclerotic plaque rupture or erosion, platelet activation and its aggregation, as well as thrombosis, are the main pathophysi‐ ological events involved in the progression from stable coronary artery disease (SCAD) to acute coronary syndrome (ACS).[1]
In this study, we attempted to investigate whether DNA methylation of selected CpG islands in the paraoxonase 1 (PON1) promoter is involved in clopidogrel resistance in Chinese CAD patients treated with clopidogrel
The phe‐ nomenon of clopidogrel resistance was influenced by many kinds of extrinsic factors and intrinsic factors that may contribute to CR.[20]
Summary
Atherosclerotic plaque rupture or erosion, platelet activation and its aggregation, as well as thrombosis, are the main pathophysi‐ ological events involved in the progression from stable coronary artery disease (SCAD) to acute coronary syndrome (ACS).[1] Dual antiplatelet treatment (usually using aspirin along with P2Y12 re‐ ceptor inhibitors, such as clopidogrel) has been the cornerstone treatment in patients after percutaneous coronary intervention (PCI). The above drugs, such as clopidogrel, could inhibit the ADP receptor, preventing sustained platelet aggregation, and lower cardiovascular risk.[2]. In this study, we attempted to investigate whether DNA methylation of selected CpG islands in the PON1 promoter is involved in clopidogrel resistance in Chinese CAD patients treated with clopidogrel
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
