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. 2019 Jun;33(5):e22867.
doi: 10.1002/jcla.22867. Epub 2019 Mar 19.

Association of PON1 gene promoter DNA methylation with the risk of Clopidogrel resistance in patients with coronary artery disease

Jia Su  1 , Jiyi Li  1 , Qinglin Yu  2 , Xiaofeng Xu  1 , Jingqiao Wang  3 , Jin Yang  1 , Xiaojing Li  1 , Xiaomin Chen  1
Affiliations

Association of PON1 gene promoter DNA methylation with the risk of Clopidogrel resistance in patients with coronary artery disease

Jia Su et al. J Clin Lab Anal. 2019 Jun.

Abstract

Background and aims: The 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.

Methods: Through 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.

Results: In 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.

Conclusions: The 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.

Keywords: PON1; DNA methylation; clopidogrel resistance; coronary artery disease.

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Figures

Figure 1
Figure 1
A comparison of PON1 gene promoter DNA methylation levels between cases and controls
Figure 2
Figure 2
A comparison of PON1 gene promoter DNA methylation levels between cases and controls in the subgroup with dyslipidemia
Figure 3
Figure 3
A comparison of PON1 mRNA expression between cases and controls in the subgroup with dyslipidemia
See this image and copyright information in PMC

References

    1. Jennings LK. Mechanisms of platelet activation: need for new strategies to protect against platelet‐mediated atherothrombosis. Thromb Haemost. 2009;102(2):248‐257. - PubMed
    1. Jneid H, Addison D, Bhatt DL, et al. 2017 AHA/ACC clinical performance and quality measures for adults with ST‐elevation and Non‐ST‐elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures. J Am Coll Cardiol. 2017;70(16):2048‐2090. - PubMed
    1. Udell JA, Bonaca MP, Collet JP, et al. Long‐term dual antiplatelet therapy for secondary prevention of cardiovascular events in the subgroup of patients with previous myocardial infarction: a collaborative meta‐analysis of randomized trials. Eur Heart J. 2016;37(4):390‐399. - PubMed
    1. Nguyen TA, Diodati JG, Pharand C. Resistance to clopidogrel: a review of the evidence. J Am Coll Cardiol. 2005;45(8):1157‐1164. - PubMed
    1. Hochholzer W, Trenk D, Bestehorn HP, et al. Impact of the degree of peri‐interventional platelet inhibition after loading with clopidogrel on early clinical outcome of elective coronary stent placement. J Am Coll Cardiol. 2006;48(9):1742‐1750. - PubMed