Li Dandan, Ling Xi, Li Xiaoqing, Wei Hongtao, Zhao Zhigang, Li Xingang, Ma Ning
Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Cerebrovasc Dis. 2022;51(6):712-721. doi: 10.1159/000524416. Epub 2022 Jun 28.
We aimed to assess whether the aberrant methylation of GNAQ gene, which may involve in the clopidogrel resistance (CR), was associated with a higher risk of recurrent ischemic events in clopidogrel-treated acute ischemic stroke or transient ischemic attack (TIA) patients.
This is a nested case-control study, 152 clopidogrel-treated acute ischemic stroke or TIA patients that were propensity-matched were included in the final analysis, including 36 patients with vascular recurrence set as cases. Methylation levels of GNAQ gene were identified with MassARRAY EpiTYPER assays. Univariate and multivariate logistic regression analyses were conducted to explore the predictive value of CpG units for recurrent ischemic events within 1 year.Mediation analysis was performed to assess the role of CR in describing the effect of GNAQ methylation on recurrent ischemic events.
A total of 16 differentially methylated CpG units were identified. Multivariate logistic analysis indicated that the average methylation of CpG 32-39 of GNAQ was associated with a significantly higher risk of ischemic events (p < 0.001). When transformed into dichotomous variables with the receiver operating characteristic curve, hypomethylation (<0.31) of CpG 32-39 of GNAQ significantly increased the risk of vascular recurrence (odds ratio 73.82, 95% confidence interval 20.33-268.01). The mediation effect of CR for recurrent ischemic events was not identified.
Hypomethylation of CpG 32-39 of GANQ gene was associated with a higher risk of ischemic events for clopidogrel-treated acute ischemic stroke or TIA patients. Further studies were warranted to explain the possible mechanism.
我们旨在评估可能与氯吡格雷抵抗（CR）相关的GNAQ基因异常甲基化是否与氯吡格雷治疗的急性缺血性卒中或短暂性脑缺血发作（TIA）患者复发性缺血事件的较高风险相关。
这是一项巢式病例对照研究，最终分析纳入了152例经倾向匹配的接受氯吡格雷治疗的急性缺血性卒中或TIA患者，其中36例发生血管复发的患者作为病例组。采用MassARRAY EpiTYPER分析法鉴定GNAQ基因的甲基化水平。进行单因素和多因素逻辑回归分析，以探讨CpG单位对1年内复发性缺血事件的预测价值。进行中介分析以评估CR在描述GNAQ甲基化对复发性缺血事件影响中的作用。
共鉴定出16个差异甲基化的CpG单位。多因素逻辑分析表明，GNAQ的CpG 32 - 39平均甲基化与缺血事件风险显著升高相关（p < 0.001）。当通过受试者工作特征曲线转换为二分变量时，GNAQ的CpG 32 - 39低甲基化（<0.31）显著增加了血管复发风险（优势比73.82，95%置信区间20.33 - 268.01）。未发现CR对复发性缺血事件的中介作用。
GANQ基因CpG 32 - 39低甲基化与氯吡格雷治疗的急性缺血性卒中或TIA患者缺血事件风险较高相关。有必要进一步研究以解释其可能机制。
