The impact of P2Y12 promoter DNA methylation on the recurrence of ischemic events in Chinese patients with ischemic cerebrovascular disease.
The primary mechanism of clopidogrel resistance is still unclear. We aimed to investigate whether the methylation status of the P2Y12 promoter has effects on platelet function and clinical ischemic events. Patients with ischemic cerebrovascular disease were enrolled into our study. Venous blood samples were drawn for thrombelastograpy (TEG) and active metabolite assay. Patients were divided into a case- or control-group based on the occurrence of ischemic events during a one year follow-up. Two TEG parameters between the case and control groups were statistically significant [ADP inhibition rate (ADP%): P = 0.018; ADP-induced platelet-fibrin clot strength (MAADP): P = 0.030]. The concentrations of clopidogrel active metabolite had no significant difference (P = 0.281). Sixteen CpG dinucleotides on P2Y12 promoter were tested. Three CpG sites (CpG11 and CpG12 + 13) showed lower methylation status, which correlated with a strong association with increased risk of clinical events. Changes of MAADPand ADP% were also associated with methylation levels of CpG 11 and CpG 12 + 13. Hypomethylation of the P2Y12 promoter is associated with a higher platelet reactivity and increased risk of ischemic events in our patients. Methylation analysis of peripheral blood samples might be a novel molecular marker to help early identification of patients at high risk for clinical ischemic events.
Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|Precision Medicine Research Center for Neurological Disorders, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Xin-Gang
XG
Li
Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Ning
N
Ma
Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Bo
B
Wang
Department of Neurology, Shaanxi Provincial People's Hospital, Xi'an, China.
Xiao-Qing
XQ
Li
Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Sheng-Hui
SH
Mei
Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Kun
K
Zhao
Precision Medicine Research Center for Neurological Disorders, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Yong-Jun
YJ
Wang
Precision Medicine Research Center for Neurological Disorders, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Wei
W
Li
Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|Precision Medicine Research Center for Neurological Disorders, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Zhi-Gang
ZG
Zhao
College of Pharmacy, Western New England University, Springfield, Massachusetts, United States of America.
Shu-Sen
SS
Sun
Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Zhong-Rong
ZR
Miao
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