Guo Y M, Zhao Z C, Zhang L, Li H Z, Li Z, Sun H L
Department of Cardiovascular Internal Medicine, Zhengzhou Central Hospital Affiliated to Zhengzhou University.
Institute of Medicine, Central South University, Changsha, China.
Genet Mol Res. 2016 May 25;15(2):gmr8012. doi: 10.4238/gmr.15028012.
The goal of this study was to explore the polymorphisms of CYP2C19 (CYP2C192, CYP2C193) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) on clopidogrel therapy in Zhengzhou city for guidance on clinical medication and reduction in the incidence of thromboembolic events. Two hundred and thirty-four ACS patients undergoing PCI were included in the study, including 171 males (average age = 64.13 ± 12 years) and 63 females (average age = 67.86 ± 10.20 years). Pyrosequencing analysis detected CYP2C192/3 genotypes, which were divided into wild-type homozygous C/C, mutant heterozygous C/T, and mutant homozygous T/T. This study further explored the relationship between CYP2C19 polymorphisms and clopidogrel resistance in ACS patients. Gene frequencies of C/C, C/T, and T/T for CYP2C192 were 39.74, 50, and 10.26%, respectively, while the frequencies of C/C, C/T, and T/T for CYP2C193 were 94.02, 5.55, and 0.43%, respectively. According to platelet aggregation analysis, 203 cases normally responded to clopidogrel (86.8%) and 31 cases were clopidogrel resistant (13.2%). There was a correlation between gender and genotype distribution but none between age and genotype. In addition, patients with clopidogrel resistance were treated with ticagrelor antiplatelet therapy instead of clopidogrel, and only 1 case in all patients suffered thrombotic events during a 3-12 month follow-up. In conclusion, CYP2C19*2/3 polymorphisms may be associated with clopidogrel resistance. Wild-type homozygote and single mutant heterozygote of CYP2C192/*3 can be given a normal dose of clopidogrel, while carriers with single mutant homozygote or double mutant heterozygote require ticagrelor antiplatelet therapy as an alternative.
本研究旨在探讨郑州市接受经皮冠状动脉介入治疗（PCI）并使用氯吡格雷治疗的急性冠状动脉综合征（ACS）患者中细胞色素P450 2C19（CYP2C192、CYP2C193）的基因多态性，以指导临床用药并降低血栓栓塞事件的发生率。本研究纳入了234例接受PCI的ACS患者，其中男性171例（平均年龄=64.13±12岁），女性63例（平均年龄=67.86±10.20岁）。焦磷酸测序分析检测CYP2C192/3基因型，分为野生型纯合子C/C、突变型杂合子C/T和突变型纯合子T/T。本研究进一步探讨了ACS患者中CYP2C19基因多态性与氯吡格雷抵抗之间的关系。CYP2C192的C/C、C/T和T/T基因型频率分别为39.74%、50%和10.26%，而CYP2C193的C/C、C/T和T/T基因型频率分别为94.02%、5.55%和0.43%。根据血小板聚集分析，203例对氯吡格雷反应正常（86.8%），31例对氯吡格雷抵抗（13.2%）。性别与基因型分布之间存在相关性，而年龄与基因型之间无相关性。此外，对氯吡格雷抵抗的患者改用替格瑞洛抗血小板治疗，而不是氯吡格雷，在3至12个月的随访期间，所有患者中仅1例发生血栓事件。总之，CYP2C19*2/3基因多态性可能与氯吡格雷抵抗有关。CYP2C192/*3的野生型纯合子和单突变杂合子可给予常规剂量的氯吡格雷，而单突变纯合子或双突变杂合子携带者则需要改用替格瑞洛抗血小板治疗。
