Zhigang Zhao1,2,3, Xingang Li2,3, Shusen Sun4, Shenghui Mei2, Ning Ma5, Zhongrong Miao5, Ming Zhao6,7,8, Shiqi Peng9,10. 1. Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China. 2. Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China. 3. Precision Medicine Research Center for Neurological Disorders, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China. 4. College of Pharmacy, Western New England University, Springfield, MA, 01109, USA. 5. Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China. 6. Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China. mingzhao@bjmu.edu.cn. 7. Faculty of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan. mingzhao@bjmu.edu.cn. 8. College of Pharmaceutical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men, Beijing, 100069, People's Republic of China. mingzhao@bjmu.edu.cn. 9. Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China. sqpeng@bjmu.edu.cn. 10. College of Pharmaceutical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men, Beijing, 100069, People's Republic of China. sqpeng@bjmu.edu.cn.
Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
PURPOSE: 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. METHODS: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. RESULTS: 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 CES1rs8192950 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. CONCLUSIONS: 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.
Authors: Hao-Jie Zhu; Kennerly S Patrick; Hong-Jie Yuan; Jun-Sheng Wang; Jennifer L Donovan; C Lindsay DeVane; Robert Malcolm; Julie A Johnson; Geri L Youngblood; Douglas H Sweet; Taimour Y Langaee; John S Markowitz Journal: Am J Hum Genet Date: 2008-05-15 Impact factor: 11.025
Authors: P A Gurbel; T O Bergmeijer; U S Tantry; J M ten Berg; D J Angiolillo; S James; T L Lindahl; P Svensson; J A Jakubowski; P B Brown; S Duvvuru; S Sundseth; J R Walker; D Small; B A Moser; K J Winters; D Erlinge Journal: Thromb Haemost Date: 2014-07-10 Impact factor: 5.249
Authors: S A Scott; K Sangkuhl; C M Stein; J-S Hulot; J L Mega; D M Roden; T E Klein; M S Sabatine; J A Johnson; A R Shuldiner Journal: Clin Pharmacol Ther Date: 2013-05-22 Impact factor: 6.875