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MiR-6076 Rs1463411 Polymorphisms Are Associated with Bleeding During Clopidogrel Treatment in Patients with Acute Coronary Syndrome

Overview
Journal Eur J Med Res
Publisher Biomed Central
Specialty General Medicine
Date 2023 Feb 24
PMID 36829258
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Abstract

Bleeding is a major adverse event during clopidogrel treatment in patients with acute coronary syndrome (ACS). However, the potential mechanism affecting bleeding among individuals is unclear. Herein, we investigated the involvement of CYP2C19*2 and CYP2C19*3, as well as 10 miRNA polymorphisms, in bleeding in Chinese patients with ACS during the first year of clopidogrel treatment. The miR-6076 rs1463411 G polymorphism was significantly associated with the risk of bleeding (P < 0.001), and the rs1463411 GT + GG genotype significantly increased the risk of bleeding (adjusted odds ratio, 6.09; 95% confidence interval, 1.09-34.0; P < 0.001). Dual luciferase assay showed that miR-6076 significantly decreased the mRNA expression of P2RY12 (P < 0.05). P2RY12 mRNA and protein levels were significantly lower in cells transfected with miR-6076-G than in cells transfected with miR-6076-T (P < 0.05). The findings indicate that miR-6076 targets P2RY12 mRNA and that miR-6076 rs1463411 T/G polymorphisms differentially regulate P2RY12 mRNA and protein levels in cells. rs1463411 G polymorphism may increase the risk of bleeding during clopidogrel treatment in patients with ACS.

References
1.
Yusuf S, Zhao F, Mehta S, Chrolavicius S, Tognoni G, Fox K . Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001; 345(7):494-502. DOI: 10.1056/NEJMoa010746. View

2.
Zhou W, Mo Z, Xiao F, Dai W, Wang G, Zhou G . microRNA-605 rs2043556 polymorphisms affect clopidogrel therapy through modulation of CYP2B6 and P2RY12 in acute coronary syndrome patients. Platelets. 2019; 31(7):897-905. DOI: 10.1080/09537104.2019.1696455. View

3.
Foster C, Prosser D, Agans J, Zhai Y, Smith M, Lachowicz J . Molecular identification and characterization of the platelet ADP receptor targeted by thienopyridine antithrombotic drugs. J Clin Invest. 2001; 107(12):1591-8. PMC: 200194. DOI: 10.1172/JCI12242. View

4.
Wallentin L, Becker R, Budaj A, Cannon C, Emanuelsson H, Held C . Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009; 361(11):1045-57. DOI: 10.1056/NEJMoa0904327. View

5.
Zhan X, Wu W, Han B, Gao G, Qiao R, Lv J . Hsa-miR-196a2 functional SNP is associated with severe toxicity after platinum-based chemotherapy of advanced nonsmall cell lung cancer patients in a Chinese population. J Clin Lab Anal. 2012; 26(6):441-6. PMC: 6807410. DOI: 10.1002/jcla.21544. View