Key result
miR-6076 rs1463411 G allele linked to a ~6-fold higher bleeding risk on clopidogrel post-ACS.
Why the study?
The mechanism underlying bleeding risk during clopidogrel treatment in patients with ACS is unclear, particularly the role of miRNA polymorphisms.
Does the miR-6076 rs1463411 polymorphism increase the risk of bleeding in Chinese patients with ACS during clopidogrel treatment?
Cohort (n=563)
Yes
Does the miR-6076 rs1463411 polymorphism increase the risk of bleeding in Chinese patients with ACS during clopidogrel treatment?
The miR-6076 rs1463411 G polymorphism significantly increases bleeding risk in Chinese ACS patients on clopidogrel by downregulating P2RY12 expression.
May flag bleeding-prone ACS patients on clopidogrel; hypothesis-generating pending validation before any clinical use.
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.
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Mo et al. (2023) conducted a cohort in Acute coronary syndrome (n=563). miR-6076 rs1463411 GT + GG genotype vs. miR-6076 rs1463411 TT genotype was evaluated on Bleeding events (BARC type 2, 3, or 5) (OR 6.09, 95% CI 1.09-34.0, p=<0.001). The miR-6076 rs1463411 GT + GG genotype significantly increased the risk of bleeding (OR 6.09) compared to the TT genotype in patients with acute coronary syndrome during clopidogrel treatment.
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