Mutational analysis clopidogrel resistance and platelet function in patients scheduled for coronary artery bypass grafting.
Mutational analysis clopidogrel resistance and platelet function in patients scheduled for coronary artery bypass grafting.
复制标题
计划进行冠状动脉旁路移植术的患者的氯吡格雷抵抗和血小板功能的突变分析。
DOI：
10.1016/j.ygeno.2013.01.005
复制
发表时间：
2013
期刊：
影响因子：
4.4
通讯作者：
Grau,JuanB
中科院分区：
文献类型：
--
作者：
Correll,Mick;Johnson,ChristopherK;Ferrari,Giovanni;Brizzio,Mariano;Mak,AndrewWC;Quackenbush,John;Shaw,RichardE;Zapolanski,Alex;Grau,JuanB
氯吡格雷是一种口服抗血小板前体药物，全球有4000万有血栓形成风险或正在接受经皮冠状动脉介入治疗（PCI）的患者。然而，大约五分之一的患者接受氯吡格雷治疗后对药物反应不佳。从105名患者的队列中，我们有氯吡格雷反应的功能数据，我们使用超高通量测序来检测CYP2C19和ABCB 1的突变，这两个基因与反应相关。根据FDA的建议，检测CYP2C19的突变只能正确预测患者对氯吡格雷的反应率为52.4%。同样，ABCB1基因检测仅正确预测了51例（48.6%）患者的反应。这些结果具有临床相关性，并表明在发现其他遗传因素更完全地预测反应之前，功能测定更适合临床使用。
Clopidogrel is an oral antiplatelet pro-drug prescribed to 40million patients worldwide who are at risk for thrombotic events or receiving percutaneous coronary intervention (PCI). However about a fifth of patients treated with clopidogrel do not respond adequately to the drug. From a cohort of 105 patients on whom we had functional data on clopidogrel response, we used ultra-high throughput sequencing to assay mutations in CYP2C19 and ABCB1, the two genes genetically linked to respond. Testing for mutations in CYP2C19, as recommended by the FDA, only correctly predicted if a patient would respond to clopidogrel 52.4% of the time. Similarly, testing of the ABCB1 gene only correctly foretold response in 51 (48.6%) patients. These results are clinically relevant and suggest that until additional genetic factors are discovered that predict response more completely, functional assays are more appropriate for clinical use.