Association of PON1 gene promoter DNA methylation with the risk of clopidogrel poor response in patients with coronary artery disease

[GW30-e0053]

Authors: Jia Su, Xiaomin Chen

Department of Cardiology, Ningbo No. 1 Hospital, Ningbo, Zhejiang, P.R. China

OBJECTIVES 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 analysed by quantitative real-time PCR. Logistic regression was applied to investigate the interatcion of PON1 methylation and clinical -factors in CR.

RESULTS In the subgroup with dyslipidaemia, we discovered that higher CpG4 levels of the PON1 promoter indicated a poorer clopidogrel response (cases versus controls (%): 51.500±14.742 versus 43.308±10.891, =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 with 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 dyslipidaemia, and the number of stents might be a risk for CR.