羧肽酶 1 S75N 对急性冠脉综合征患者氯吡格雷治疗的影响。
Effect of carboxylesterase 1 S75N on clopidogrel therapy among acute coronary syndrome patients.
机构信息
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, China.
Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha, China.
出版信息
Sci Rep. 2017 Aug 3;7(1):7244. doi: 10.1038/s41598-017-07736-1.
Carboxylesterase 1 (CES1) hydrolyzes the prodrug clopidogrel to an inactive carboxylic acid metabolite. The effects of CES1 S75N (rs2307240,C>T) on clopidogrel response among 851 acute coronary syndrome patients who came from the north, central and south of China were studied. The occurrence ratios of each endpoint in the CC group were significantly higher than in the CT + TT group for cerebrovascular events (14% vs 4.8%, p < 0.001, OR = 0.31), acute myocardial infarction (15.1% vs 6.1%, p < 0.001, OR = 0.37) and unstable angina (62.8% vs 37.7%, p < 0.001, OR = 0.36). The results showed that there was a significant association between CES1 S75N (rs2307240) and the outcome of clopidogrel therapy. Moreover, the frequency of the T allele of rs2307240 in acute coronary syndrome patients (MAF = 0.22) was more than four times higher than that in the general public (MAF = 0.05).
羧酸酯酶 1（CES1）将前药氯吡格雷水解为无活性的羧酸代谢物。在中国北方、中部和南方的 851 例急性冠脉综合征患者中，研究了 CES1 S75N（rs2307240，C>T）对氯吡格雷反应的影响。CC 组中每个终点的发生率明显高于 CT+TT 组，其中脑血管事件（14%比 4.8%，p<0.001，OR=0.31）、急性心肌梗死（15.1%比 6.1%，p<0.001，OR=0.37）和不稳定型心绞痛（62.8%比 37.7%，p<0.001，OR=0.36）。结果表明，CES1 S75N（rs2307240）与氯吡格雷治疗的结果有显著相关性。此外，急性冠脉综合征患者中 rs2307240 的 T 等位基因频率（MAF=0.22）比普通人群（MAF=0.05）高出四倍以上。
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