MiR-6076 rs1463411 polymorphisms are associated with bleeding during clopidogrel treatment in patients with acute coronary syndrome

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.