Related Experiment Video
Updated: Sep 6, 2025
Assessing Neuroprotective Effects of Glycyrrhizae Radix et Rhizoma Extract Using a Transient Middle Cerebral Artery Occlusion Mouse Model
Published on: December 9, 2018
Association between GNAQ Gene DNA Methylation and Vascular Recurrence in Patients with Acute Ischemic Stroke or
Dandan Li1, Xi Ling2, Xiaoqing Li3,4
1Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Insights
Hypomethylation of the GNAQ gene in patients treated with clopidogrel for acute ischemic stroke or TIA is linked to an increased risk of recurrent ischemic events. This finding may inform risk stratification for these patients.
Area of Science:
- Genetics and Epigenetics
- Cardiovascular Medicine
- Neurology
Background:
- Clopidogrel is a key antiplatelet medication for acute ischemic stroke and transient ischemic attack (TIA).
- Clopidogrel resistance (CR) is a clinical concern, potentially increasing the risk of recurrent vascular events.
- Aberrant gene methylation, specifically of the GNAQ gene, has been implicated as a potential factor in CR.
Purpose of the Study:
- To investigate the association between GNAQ gene methylation patterns and the risk of recurrent ischemic events in patients treated with clopidogrel.
- To determine if GNAQ gene methylation could serve as a predictive biomarker for vascular recurrence.
Main Methods:
- A nested case-control study involving 152 clopidogrel-treated patients with acute ischemic stroke or TIA.
- Propensity score matching was used to control for confounding factors.
- GNAQ gene methylation levels were quantified using MassARRAY EpiTYPER assays.
- Logistic regression and mediation analyses were performed to assess the relationship between methylation, CR, and recurrent events.
Main Results:
- Sixteen differentially methylated CpG units of the GNAQ gene were identified.
- Hypomethylation of GNAQ CpG 32-39 was significantly associated with an increased risk of ischemic events (p < 0.001).
- Receiver operating characteristic curve analysis revealed that hypomethylation (<0.31) of GNAQ CpG 32-39 strongly predicted vascular recurrence (OR 73.82).
- Clopidogrel resistance did not mediate the effect of GNAQ methylation on recurrent events.
Conclusions:
- Hypomethylation of the GNAQ gene, particularly at CpG sites 32-39, is a significant risk factor for recurrent ischemic events in clopidogrel-treated patients.
- GNAQ gene methylation may represent a novel biomarker for predicting vascular events in this population.
- Further research is needed to elucidate the underlying mechanisms connecting GNAQ methylation to ischemic risk and clopidogrel response.
Purpose:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
More Related Videos
11:19Correlating Gene-specific DNA Methylation Changes with Expression and Transcriptional Activity of Astrocytic KCNJ10 Kir4.1
Published on: September 26, 2015
05:40AAV Systems and Mouse Models for Investigating Ectopic Expression of Neurod1 in Transduced Cells at Subacute and Chronic Times Post-Ischemic Stroke
Published on: November 29, 2024
