Liu Xu, Luo Yu, Lai Yan, Yao Yian, Li Jimin, Wang Yunkai, Zheng S Lilly, Xu Jianfeng, Liu Xuebo
State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology,and School of Life Sciences, Fudan University, Shanghai 200433, People's Republic of
J Genet. 2016 Jun;95(2):231-7. doi: 10.1007/s12041-016-0618-1.
Polymorphisms of CYP2C19 are associated with platelet response to clopidogrel. This study was conducted to evaluate the contribution of the previously identified polymorphisms to the response of clopidogrel in a cohort of Chinese Han patients. A total of 222 acute coronary syndrome patients undergoing percutaneous coronary intervention treated with clopidogrel were enrolled from September 2012 to June 2013. Residual platelet aggregations for all patients were measured by the Verify Now P2Y12 system. Sixteen single-nucleotide polymorphisms among nine genes were genotyped including CYP2C19, ABCB1 and PON1. In this study, CYP2C192 and CYP2C1917 were strongly associated with higher platelet aggregation and lower platelet aggregation to clopidogrel treatment, respectively (P <0.001). Patients with CYP2C192 allele had a higher risk of high on-treatment platelet reactivity than non carriers (adjusted OR, 5.434; 95% CI, 1.918-15.399, P =0.01). The coexistence of CYP2B69 (rs8192719) and P2Y12 (rs2046934) and the coexistence of CYP2B61B (rs7254579) and P2Y12 (rs2046934) were also associated with poor response to clopidogrel. No significant relation of CYP2C193 and other polymorphisms to the platelet aggregation was found. In conclusion, CYP2C192, CYP2C1917 coexistence of CYP2B69 (rs8192719) and P2Y12 (rs2046934) and coexistence of CYP2B61B (rs7254579) and P2Y12 (rs2046934) were identified to be associated with response to clopidogrel treatment in Chinese Han patients.
细胞色素P450 2C19(CYP2C19)基因多态性与血小板对氯吡格雷的反应相关。本研究旨在评估先前鉴定出的基因多态性对一组中国汉族患者氯吡格雷反应的影响。2012年9月至2013年6月,共纳入222例接受经皮冠状动脉介入治疗并服用氯吡格雷的急性冠状动脉综合征患者。所有患者的残余血小板聚集情况通过Verify Now P2Y12系统进行检测。对包括CYP2C19、ABCB1和对氧磷酶1(PON1)在内的9个基因中的16个单核苷酸多态性进行基因分型。在本研究中,CYP2C192和CYP2C1917分别与较高的血小板聚集以及对氯吡格雷治疗较低的血小板聚集密切相关(P<0.001)。携带CYP2C192等位基因的患者出现治疗中高血小板反应性的风险高于非携带者(校正比值比,5.434;95%可信区间,1.918 - 15.399,P = 0.01)。CYP2B69(rs8192719)与P2Y12(rs2046934)共存以及CYP2B61B(rs7254579)与P2Y12(rs2046934)共存也与氯吡格雷反应不佳相关。未发现CYP2C193及其他多态性与血小板聚集有显著关联。总之,在中国汉族患者中,CYP2C192、CYP2C1917、CYP2B69(rs8192719)与P2Y12(rs2046934)共存以及CYP2B61B(rs7254579)与P2Y12(rs2046934)共存被确定与氯吡格雷治疗反应相关。