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Published on: September 16, 2017
Correlation Between MMP9 Promoter Methylation and Transient Ischemic Attack/Mild Ischemic Stroke with Early Cognitive
Meng Miao1, Mingyang Lyu2, Chi Zhong1
1Department of Neurology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, People's Republic of China.
Background/Objective:
Dyskinesia caused by transient ischemic attack (TIA) and mild ischemic stroke (MIS) is mild and short-lived; however, cognitive impairment (CI) can occur in the acute phase and be easily overlooked. DNA methylation is an epigenetic phenomenon that can affect gene expression through gene silencing. Blood levels of matrix metalloproteinase (MMP) 9 are elevated in ischemic stroke patients and is associated with the destruction of the blood-brain barrier and the occurrence of CI. No studies have investigated the relationship between MMP9 gene methylation and TIA/MIS with early cognitive impairment (ECI). As such, the purpose of the present study was to investigate the correlation between MMP9 gene methylation and TIA/MIS with ECI.
Methods:
Data from 112 subjects were collected, including 84 with TIA/MIS (National Institutes of Health Stroke Scale <5 points) and 28 non-stroke control subjects. Patients were evaluated within 7 days of TIA/MIS onset according to four single-domain cognitive scales. Whole blood DNA methylation was detected using MethylTarget sequencing technology. Comparison of MMP9 gene methylation levels among subgroups was performed using statistical methods.
Results:
The site S33-79 in the TIA/MIS group was hypomethylated compared with the control group, and sites S33-25 and S33-30 in TIA/MIS with ECI was hypomethylated compared with TIA/MIS without ECI. Compared with the small artery occlusion group, MMP9 gene, S33-25, 30, 39, 53, 58, 73, 79, 113 and 131 sites in the large artery atherosclerosis group were hypomethylated.
Conclusion:
MMP9 gene hypomethylation sites were associated with TIA/MIS and TIA/MIS with ECI, and there was a strong correlation between MMP9 gene hypomethylation and atherosclerotic TIA/MIS. MMP9 gene methylation can reflect the severity of TIA/MIS. MMP9 gene hypomethylation sites may be used as potential biomarkers and therapeutic targets for TIA/MIS and TIA/MIS with ECI.
Insights
Hypomethylation of the MMP9 gene is linked to transient ischemic attack (TIA) and mild ischemic stroke (MIS) with early cognitive impairment (ECI). These MMP9 gene hypomethylation sites may serve as biomarkers for TIA/MIS and ECI.
Area of Science:
- Neuroscience
- Epigenetics
- Vascular Neurology
Background:
- Transient ischemic attack (TIA) and mild ischemic stroke (MIS) can cause cognitive impairment (CI), often overlooked in the acute phase.
- Matrix metalloproteinase (MMP) 9 levels are elevated in ischemic stroke, correlating with blood-brain barrier damage and CI.
- The relationship between MMP9 gene methylation and TIA/MIS with early cognitive impairment (ECI) remains uninvestigated.
Purpose of the Study:
- To investigate the correlation between MMP9 gene methylation and TIA/MIS with ECI.
- To explore MMP9 gene methylation as a potential indicator for cognitive impairment following TIA/MIS.
Main Methods:
- Collected data from 112 subjects (84 TIA/MIS, 28 controls), assessing cognition within 7 days of onset.
- Utilized MethylTarget sequencing technology to detect whole blood DNA methylation.
- Performed statistical comparisons of MMP9 gene methylation levels across subgroups.
Main Results:
- Hypomethylation at site S33-79 observed in the TIA/MIS group compared to controls.
- Sites S33-25 and S33-30 were hypomethylated in TIA/MIS with ECI compared to TIA/MIS without ECI.
- Significant hypomethylation of multiple MMP9 gene sites (including S33-25, 30, 39, 53, 58, 73, 79, 113, 131) was found in the large artery atherosclerosis group compared to small artery occlusion.
Conclusions:
- MMP9 gene hypomethylation sites are associated with TIA/MIS and ECI.
- A strong correlation exists between MMP9 gene hypomethylation and atherosclerotic TIA/MIS.
- MMP9 gene hypomethylation sites show potential as biomarkers and therapeutic targets for TIA/MIS and ECI.
