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Updated: Mar 7, 2026
Correlating Gene-specific DNA Methylation Changes with Expression and Transcriptional Activity of Astrocytic KCNJ10 Kir4.1
Published on: September 26, 2015
Methylation in the matrix metalloproteinase-2 gene is associated with cerebral ischemic stroke
Hsiu-Fen Lin1,2, Edward Hsi3,4, Ling-Chun Huang1
1Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Abstract:
Matrix metalloproteinase-2 (MMP-2) is involved in the pathophysiology of stroke. Previous studies have shown that MMP-2 activity is increased in stroke; however, evidence of epigenetic regulation of the MMP-2 in stroke is still limited. We examined methylation of the MMP-2 promoter in patients with ischemic stroke. This study included 298 patients with ischemic stroke and 258 age-matched and sex-matched controls. MMP-2 promoter methylation levels were measured by pyrosequencing at eight potential cytosine-guanine (CpG) sites. Multivariate regression analysis was used to adjust for general stroke risk factors, and the specific effects of sex and stroke subtype were analysed. The methylation levels of MMP-2 in the peripheral blood of the patients with stroke were lower than controls in all eight CpG sites, especially at site 1, site 5, site 7, and site 8 (adjusted p=0.036, 0.002, 0.021, and 0.041, respectively). In subgroup analysis by sex, a significant association was found only in men but not in women. When the stroke subtype was considered, men with small-vessel stroke had significantly lower methylation levels at all MMP-2 CpG sites than the controls (3.01% vs 3.65%, adjusted p=0.018). Although men with large-artery atherosclerosis stroke also had lower MMP-2 methylation levels, no significant difference was found (3.25% vs 3.65%, adjusted p=0.253). Demethylation of the MMP-2 promoter in patients with ischemic stroke was in a sex and stroke subtype-specific manners. These findings may add to the understanding of epigenetic modification of MMP-2 on ischemic stroke.
Insights
Epigenetic changes in matrix metalloproteinase-2 (MMP-2) promoter methylation are linked to ischemic stroke, particularly in men and specific stroke subtypes. Lower MMP-2 promoter methylation was observed in stroke patients, suggesting a role in stroke pathophysiology.
Area of Science:
- Neuroscience
- Genetics
- Biochemistry
Background:
- Matrix metalloproteinase-2 (MMP-2) plays a role in stroke pathophysiology, with elevated activity observed in stroke patients.
- Epigenetic regulation, specifically DNA methylation, of MMP-2 in stroke remains under-investigated.
- Understanding MMP-2's epigenetic modifications can offer new insights into stroke mechanisms.
Purpose of the Study:
- To investigate the methylation status of the MMP-2 promoter in patients with ischemic stroke.
- To determine if MMP-2 promoter methylation differs between ischemic stroke patients and healthy controls.
- To explore the influence of sex and stroke subtype on MMP-2 promoter methylation.
Main Methods:
- A case-control study involving 298 ischemic stroke patients and 258 controls.
- MMP-2 promoter methylation was quantified at eight CpG sites using pyrosequencing.
- Multivariate regression analysis adjusted for stroke risk factors, with subgroup analyses for sex and stroke subtype.
Main Results:
- Ischemic stroke patients exhibited lower MMP-2 promoter methylation across all eight CpG sites compared to controls.
- Significant hypomethylation was particularly noted at CpG sites 1, 5, 7, and 8.
- The association between lower MMP-2 methylation and stroke was significant in men but not women.
- Men with small-vessel stroke showed significantly reduced MMP-2 methylation at all sites compared to controls.
Conclusions:
- Demethylation of the MMP-2 promoter in ischemic stroke occurs in a sex- and stroke subtype-specific manner.
- These findings highlight the potential role of epigenetic modifications in the pathogenesis of ischemic stroke.
- The results contribute to a deeper understanding of MMP-2's epigenetic regulation in the context of stroke.
