Epigenetic interaction of miRNA-26a and P2Y12 gene DNA methylation on platelet reactivity under clopidogrel and their impact to the coronary flow after primary PCI in STEMI

Abstract

Abstract Background Epigenetic factors such as miRNA-26A and P2Y12 DNA methylation play role in pathophysiology of cardiovascular disease. Clopidogrel-resistance is associated with worse cardiovascular outcome. The interactions between the expression of platelet miRNA-26a and P2Y12 DNA methylation to clopidogrel resistance and post procedural TIMI flow in STEMI patients undergoing primary PCI is unclear. Purpose To define interaction of epigenetic factors micro-RNA (miRNA)-26a expression and P2Y12 gene DNA methylation to the platelet reactivity under clopidogrel therapy, and their impact on the coronary flow after Primary PCI in patients with STEMI. Methods We studied STEMI patients who underwent primary PCI, receiving 600 mg loading dose of clopidogrel. Platelet reactivity assessed by VerifyNow P2Y12. Realtime PCR was performed to measure the expression of platelet miR-26a and DNA methylation of P2Y12 gene. Postprocedural epicardial coronary flow was assessed semi quantitatively. Results There were 100 patients were recruited. Among them, 59% have high miRNA-26a platelet expression, 60% had no methylation in their P2Y12 gene, and 27% had high platelet reactivity index under clopidogrel therapy. There was association between high miR-26a expression and reduced platelet inhibition under clopidogrel (OR 4.2, p<0.01), but not with DNA methylation of P2Y12 gene. High platelet reactivity index under clopidogrel therapy was associated with suboptimal coronary flow after primary PCI in STEMI patients (OR 3.3, p<0.05). Conclusions High miRNA-26a platelet expression, but not DNA methylation of P2Y12 gene, in patients with acute STEMI have significant association with high platelet reactivity under clopidogrel therapy. Furthermore, high platelet reactivity under clopidogrel is associated with suboptimal coronary flow in STEMI patients undergoing primary PCI. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Harapan Kita Honor Research Grant