Impact of genetic polymorphisms related to clopidogrel or acetylsalicylic acid pharmacology on clinical outcome in Chinese patients with symptomatic extracranial or intracranial stenosis
机构:[1]Capital Med Univ, Beijing Area Major Lab Peptide & Small Mol Drugs, Engn Res Ctr Endogenous Prophylact, Minist Educ China,Beijing Lab Biomed Mat,Coll Pha, Beijing, Peoples R China;[2]Capital Med Univ, Beijing Tiantan Hosp, Dept Pharm, Beijing, Peoples R China;职能科室医技科室药学部药学部/药剂科首都医科大学附属天坛医院[3]Capital Med Univ, Beijing Tiantan Hosp, Precis Med Res Ctr Neurol Disorders, Beijing, Peoples R China;重点科室诊疗科室神经病学中心神经病学中心首都医科大学附属天坛医院[4]Western New England Univ, Coll Pharm, Springfield, MA 01109 USA;[5]Capital Med Univ, Beijing Tiantan Hosp, Dept Intervent Neuroradiol, Beijing, Peoples R China;重点科室医技科室放射科放射科首都医科大学附属天坛医院[6]Kaohsiung Med Univ, Fac Biomed Sci & Environm Biol, Kaohsiung, Taiwan;[7]Capital Med Univ, Coll Pharmaceut Sci, 10 Xitoutiao, Beijing 100069, Peoples R China
Recurrent ischemic events in Chinese patients with symptomatic extracranial or intracranial stenosis caused by aspirin or clopidogrel resistance are well known. We aimed to identify the contribution of genetic variants to the events. Patients with symptomatic extracranial or intracranial stenosis receiving dual antiplatelet treatment for at least 5 days were enrolled in this study. The primary endpoint was a composite of ischemic events, including recurrent transient ischemic attack, stroke, myocardial infarction, and vascular-related mortality. Twenty-four single nucleotide polymorphisms (SNPs) were assessed and genotyped. The clinical characteristics of enrolled patients were collected from medical records. The influence of genetic polymorphisms on the recurrent ischemic events of the patients was examined. A total of 377 patients were included. During a 12-month follow-up, the composite primary endpoint was observed in 64 patients. The CYP2C19*3 (rs4986893) may increase the occurrence of the primary composite endpoint (OR = 2.56, 95 % CI = 1.29-5.10, P = 0.007), and the mutation of CES1 rs8192950 was associated with the decreased recurrence of ischemic events (OR = 0.53, 95 % CI = 0.30-0.94, P = 0.029). The other SNPs that were tested did not have statistically significant associations with the composite endpoint. For Chinese patients with symptomatic extracranial or intracranial stenosis treated with clopidogrel, CYP2C19*3 mutation was associated with an increased risk of ischemic events, and the mutation of rs8192950 in CES1 is associated with a decreased risk of recurrent ischemic events. Testing these two SNPs could be of value in the identification of patients at risk for recurrent ischemic events.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81503157, 81373264]; Organization Department of Beijing Municipal Committee [2014000021469G258]; Capital Medical University [16JL72]
第一作者机构:[1]Capital Med Univ, Beijing Area Major Lab Peptide & Small Mol Drugs, Engn Res Ctr Endogenous Prophylact, Minist Educ China,Beijing Lab Biomed Mat,Coll Pha, Beijing, Peoples R China;[2]Capital Med Univ, Beijing Tiantan Hosp, Dept Pharm, Beijing, Peoples R China;[3]Capital Med Univ, Beijing Tiantan Hosp, Precis Med Res Ctr Neurol Disorders, Beijing, Peoples R China;
通讯作者:
通讯机构:[1]Capital Med Univ, Beijing Area Major Lab Peptide & Small Mol Drugs, Engn Res Ctr Endogenous Prophylact, Minist Educ China,Beijing Lab Biomed Mat,Coll Pha, Beijing, Peoples R China;[6]Kaohsiung Med Univ, Fac Biomed Sci & Environm Biol, Kaohsiung, Taiwan;[7]Capital Med Univ, Coll Pharmaceut Sci, 10 Xitoutiao, Beijing 100069, Peoples R China
推荐引用方式(GB/T 7714):
Zhao Zhigang,Li Xingang,Sun Shusen,et al.Impact of genetic polymorphisms related to clopidogrel or acetylsalicylic acid pharmacology on clinical outcome in Chinese patients with symptomatic extracranial or intracranial stenosis[J].EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY.2016,72(10):1195-1204.doi:10.1007/s00228-016-2094-1.
APA:
Zhao, Zhigang,Li, Xingang,Sun, Shusen,Mei, Shenghui,Ma, Ning...&Peng, Shiqi.(2016).Impact of genetic polymorphisms related to clopidogrel or acetylsalicylic acid pharmacology on clinical outcome in Chinese patients with symptomatic extracranial or intracranial stenosis.EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY,72,(10)
MLA:
Zhao, Zhigang,et al."Impact of genetic polymorphisms related to clopidogrel or acetylsalicylic acid pharmacology on clinical outcome in Chinese patients with symptomatic extracranial or intracranial stenosis".EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY 72..10(2016):1195-1204