Department of Geriatrics, National Geriatrics Clinic Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, People's Republic of China.
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, 410008, People's Republic of China.
Eur J Med Res. 2023 Feb 24;28(1):96. doi: 10.1186/s40001-023-01068-9.
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.
出血是急性冠脉综合征（ACS）患者氯吡格雷治疗中的主要不良事件。然而，影响个体出血的潜在机制尚不清楚。在此，我们研究了 CYP2C192 和 CYP2C193 以及 10 个 miRNA 多态性在 ACS 患者氯吡格雷治疗第一年出血中的作用。miR-6076 rs1463411 G 多态性与出血风险显著相关（P<0.001），rs1463411 GT+GG 基因型显著增加出血风险（调整比值比，6.09；95%置信区间，1.09-34.0；P<0.001）。双荧光素酶报告基因实验显示，miR-6076 显著降低 P2RY12 的 mRNA 表达（P<0.05）。转染 miR-6076-G 的细胞中 P2RY12 mRNA 和蛋白水平明显低于转染 miR-6076-T 的细胞（P<0.05）。研究结果表明，miR-6076 靶向 P2RY12 mRNA，miR-6076 rs1463411 T/G 多态性可差异调节细胞中 P2RY12 mRNA 和蛋白水平。rs1463411 G 多态性可能增加 ACS 患者氯吡格雷治疗中出血的风险。
