Correlation Between MMP9 Promoter Methylation and Transient Ischemic Attack/Mild Ischemic Stroke with Early Cognitive Impairment
Meng Miao,1 Mingyang Lyu,2 Chi Zhong,1 Ying Liu3 1Department of Neurology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, People’s Republic of China; 2Haihe Laboratory of Cell Ecosystem, Tianjin, People’s Republic of China; 3Department of Neurology, Qil...
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| Language: | English |
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Dove Medical Press
2023-08-01
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| Series: | Clinical Interventions in Aging |
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| Online Access: | https://www.dovepress.com/correlation-between-mmp9-promoter-methylation-and-transient-ischemic-a-peer-reviewed-fulltext-article-CIA |
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| author | Miao M Lyu M Zhong C Liu Y |
| author_facet | Miao M Lyu M Zhong C Liu Y |
| author_sort | Miao M |
| collection | DOAJ |
| description | Meng Miao,1 Mingyang Lyu,2 Chi Zhong,1 Ying Liu3 1Department of Neurology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, People’s Republic of China; 2Haihe Laboratory of Cell Ecosystem, Tianjin, People’s Republic of China; 3Department of Neurology, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Ying Liu, Department of Neurology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of China, Tel +8618005316460, Email liuyingql@163.com Chi Zhong, Department of Neurology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, 758 Hefei Road, Qingdao, Shandong, 266035, People’s Republic of China, Tel +8618561817360, Email zhong7376_cn@sina.comBackground/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.Keywords: early cognitive impairment, hypomethylation, amyloid β-protein, blood-brain barrier, MMP9 gene |
| first_indexed | 2024-03-12T20:32:26Z |
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| id | doaj.art-9281a990f5c142e6851c72571afee171 |
| institution | Directory Open Access Journal |
| issn | 1178-1998 |
| language | English |
| last_indexed | 2024-03-12T20:32:26Z |
| publishDate | 2023-08-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Clinical Interventions in Aging |
| spelling | doaj.art-9281a990f5c142e6851c72571afee1712023-08-01T19:38:39ZengDove Medical PressClinical Interventions in Aging1178-19982023-08-01Volume 181221123285582Correlation Between MMP9 Promoter Methylation and Transient Ischemic Attack/Mild Ischemic Stroke with Early Cognitive ImpairmentMiao MLyu MZhong CLiu YMeng Miao,1 Mingyang Lyu,2 Chi Zhong,1 Ying Liu3 1Department of Neurology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, People’s Republic of China; 2Haihe Laboratory of Cell Ecosystem, Tianjin, People’s Republic of China; 3Department of Neurology, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Ying Liu, Department of Neurology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of China, Tel +8618005316460, Email liuyingql@163.com Chi Zhong, Department of Neurology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, 758 Hefei Road, Qingdao, Shandong, 266035, People’s Republic of China, Tel +8618561817360, Email zhong7376_cn@sina.comBackground/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.Keywords: early cognitive impairment, hypomethylation, amyloid β-protein, blood-brain barrier, MMP9 genehttps://www.dovepress.com/correlation-between-mmp9-promoter-methylation-and-transient-ischemic-a-peer-reviewed-fulltext-article-CIAearly cognitive impairmenthypomethylationamyloid β-proteinblood-brain barriermmp9 gene. |
| spellingShingle | Miao M Lyu M Zhong C Liu Y Correlation Between MMP9 Promoter Methylation and Transient Ischemic Attack/Mild Ischemic Stroke with Early Cognitive Impairment Clinical Interventions in Aging early cognitive impairment hypomethylation amyloid β-protein blood-brain barrier mmp9 gene. |
| title | Correlation Between MMP9 Promoter Methylation and Transient Ischemic Attack/Mild Ischemic Stroke with Early Cognitive Impairment |
| title_full | Correlation Between MMP9 Promoter Methylation and Transient Ischemic Attack/Mild Ischemic Stroke with Early Cognitive Impairment |
| title_fullStr | Correlation Between MMP9 Promoter Methylation and Transient Ischemic Attack/Mild Ischemic Stroke with Early Cognitive Impairment |
| title_full_unstemmed | Correlation Between MMP9 Promoter Methylation and Transient Ischemic Attack/Mild Ischemic Stroke with Early Cognitive Impairment |
| title_short | Correlation Between MMP9 Promoter Methylation and Transient Ischemic Attack/Mild Ischemic Stroke with Early Cognitive Impairment |
| title_sort | correlation between mmp9 promoter methylation and transient ischemic attack mild ischemic stroke with early cognitive impairment |
| topic | early cognitive impairment hypomethylation amyloid β-protein blood-brain barrier mmp9 gene. |
| url | https://www.dovepress.com/correlation-between-mmp9-promoter-methylation-and-transient-ischemic-a-peer-reviewed-fulltext-article-CIA |
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