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

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 CYP2C192 and CYP2C193, 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.