Relationship between cognitive dysfunction and the promoter methylation of PER1 and CRY1 in patients with cerebral small vessel disease
Background and purposeThe prevalence of cerebral small vessel disease (CSVD) is increasing due to the accelerating global aging process, resulting in a substantial burden on all countries, as cognitive dysfunction associated with CSVD is also on the rise. Clock genes have a significant impact on cog...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2023.1174541/full |
| _version_ | 1797821458828754944 |
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| author | Yiwen Xu Yugang Wang Yi Jiang Mengqian Liu Wen Zhong Zhonglin Ge Zhichao Sun Xiaozhu Shen |
| author_facet | Yiwen Xu Yugang Wang Yi Jiang Mengqian Liu Wen Zhong Zhonglin Ge Zhichao Sun Xiaozhu Shen |
| author_sort | Yiwen Xu |
| collection | DOAJ |
| description | Background and purposeThe prevalence of cerebral small vessel disease (CSVD) is increasing due to the accelerating global aging process, resulting in a substantial burden on all countries, as cognitive dysfunction associated with CSVD is also on the rise. Clock genes have a significant impact on cognitive decline and dementia. Furthermore, the pattern of DNA methylation in clock genes is strongly associated with cognitive impairment. Thus, the aim of this study was to explore the connection between DNA promoter methylation of PER1 and CRY1 and cognitive dysfunction in patients with CSVD.MethodsWe recruited patients with CSVD admitted to the Geriatrics Department of the Lianyungang Second People’s Hospital between March 2021 and June 2022. Based on their Mini-Mental State Examination score, patients were categorized into two groups: 65 cases with cognitive dysfunction and 36 cases with normal cognitive function. Clinical data, 24-h ambulatory blood pressure monitoring parameters, and CSVD total load scores were collected. Moreover, we employed methylation-specific PCR to analyze the peripheral blood promoter methylation levels of clock genes PER1 and CRY1 in all CSVD patients who were enrolled. Finally, we used binary logistic regression models to assess the association between the promoter methylation of clock genes (PER1 and CRY1) and cognitive dysfunction in patients with CSVD.Results(1) A total of 101 individuals with CSVD were included in this study. There were no statistical differences between the two groups in baseline clinical data except MMSE and AD8 scores. (2) After B/H correction, the promoter methylation rate of PER1 was higher in the cognitive dysfunction group than that in the normal group, and the difference was statistically significant (adjusted p < 0.001). (3) There was no significant correlation between the promoter methylation rates of PER1 and CRY1 in peripheral blood and circadian rhythm of blood pressure (p > 0.05). (4) Binary logistic regression models showed that the influence of promoter methylation of PER1 and CRY1 on cognitive dysfunction were statistically significant in Model 1 (p < 0.001; p = 0.025), and it still existed after adjusting for confounding factors in Model 2. Patients with the promoter methylation of PER1 gene (OR = 16.565, 95%CI, 4.057–67.628; p < 0.001) and the promoter methylation of CRY1 gene (OR = 6.017, 95%CI, 1.290–28.069; p = 0.022) were at greater risk of cognitive dysfunction compared with those with unmethylated promoters of corresponding genes in Model 2.ConclusionThe promoter methylation rate of PER1 gene was higher in the cognitive dysfunction group among CSVD patients. And the hypermethylation of the promoters of clock genes PER1 and CRY1 may be involved in affecting cognitive dysfunction in patients with CSVD. |
| first_indexed | 2024-03-13T09:53:00Z |
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| id | doaj.art-dd9a64dec20b4778a6d1f62dcf496c83 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-03-13T09:53:00Z |
| publishDate | 2023-05-01 |
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| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-dd9a64dec20b4778a6d1f62dcf496c832023-05-24T05:41:47ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652023-05-011510.3389/fnagi.2023.11745411174541Relationship between cognitive dysfunction and the promoter methylation of PER1 and CRY1 in patients with cerebral small vessel diseaseYiwen Xu0Yugang Wang1Yi Jiang2Mengqian Liu3Wen Zhong4Zhonglin Ge5Zhichao Sun6Xiaozhu Shen7Department of Geriatrics, Lianyungang Hospital Affiliated to Jiangsu University (Lianyungang Second People’s Hospital), Lianyungang, ChinaDepartment of Neurology, The First People’s Hospital of XianYang, XianYang, ChinaDepartment of Geriatrics, Lianyungang Hospital Affiliated to Bengbu University (Lianyungang Second People’s Hospital), Lianyungang, ChinaDepartment of Geriatrics, Lianyungang Hospital Affiliated to Jiangsu University (Lianyungang Second People’s Hospital), Lianyungang, ChinaDepartment of Geriatrics, Lianyungang Hospital Affiliated to Jiangsu University (Lianyungang Second People’s Hospital), Lianyungang, ChinaDepartment of Neurology, Lianyungang Second People′s Hospital, Lianyungang, ChinaDepartment of Pathology, Lianyungang Second People′s Hospital, Lianyungang, ChinaDepartment of Geriatrics, Lianyungang Hospital Affiliated to Jiangsu University (Lianyungang Second People’s Hospital), Lianyungang, ChinaBackground and purposeThe prevalence of cerebral small vessel disease (CSVD) is increasing due to the accelerating global aging process, resulting in a substantial burden on all countries, as cognitive dysfunction associated with CSVD is also on the rise. Clock genes have a significant impact on cognitive decline and dementia. Furthermore, the pattern of DNA methylation in clock genes is strongly associated with cognitive impairment. Thus, the aim of this study was to explore the connection between DNA promoter methylation of PER1 and CRY1 and cognitive dysfunction in patients with CSVD.MethodsWe recruited patients with CSVD admitted to the Geriatrics Department of the Lianyungang Second People’s Hospital between March 2021 and June 2022. Based on their Mini-Mental State Examination score, patients were categorized into two groups: 65 cases with cognitive dysfunction and 36 cases with normal cognitive function. Clinical data, 24-h ambulatory blood pressure monitoring parameters, and CSVD total load scores were collected. Moreover, we employed methylation-specific PCR to analyze the peripheral blood promoter methylation levels of clock genes PER1 and CRY1 in all CSVD patients who were enrolled. Finally, we used binary logistic regression models to assess the association between the promoter methylation of clock genes (PER1 and CRY1) and cognitive dysfunction in patients with CSVD.Results(1) A total of 101 individuals with CSVD were included in this study. There were no statistical differences between the two groups in baseline clinical data except MMSE and AD8 scores. (2) After B/H correction, the promoter methylation rate of PER1 was higher in the cognitive dysfunction group than that in the normal group, and the difference was statistically significant (adjusted p < 0.001). (3) There was no significant correlation between the promoter methylation rates of PER1 and CRY1 in peripheral blood and circadian rhythm of blood pressure (p > 0.05). (4) Binary logistic regression models showed that the influence of promoter methylation of PER1 and CRY1 on cognitive dysfunction were statistically significant in Model 1 (p < 0.001; p = 0.025), and it still existed after adjusting for confounding factors in Model 2. Patients with the promoter methylation of PER1 gene (OR = 16.565, 95%CI, 4.057–67.628; p < 0.001) and the promoter methylation of CRY1 gene (OR = 6.017, 95%CI, 1.290–28.069; p = 0.022) were at greater risk of cognitive dysfunction compared with those with unmethylated promoters of corresponding genes in Model 2.ConclusionThe promoter methylation rate of PER1 gene was higher in the cognitive dysfunction group among CSVD patients. And the hypermethylation of the promoters of clock genes PER1 and CRY1 may be involved in affecting cognitive dysfunction in patients with CSVD.https://www.frontiersin.org/articles/10.3389/fnagi.2023.1174541/fullclock genesPER1CRY1methylationcognitive dysfunctioncerebral small vessel disease |
| spellingShingle | Yiwen Xu Yugang Wang Yi Jiang Mengqian Liu Wen Zhong Zhonglin Ge Zhichao Sun Xiaozhu Shen Relationship between cognitive dysfunction and the promoter methylation of PER1 and CRY1 in patients with cerebral small vessel disease Frontiers in Aging Neuroscience clock genes PER1 CRY1 methylation cognitive dysfunction cerebral small vessel disease |
| title | Relationship between cognitive dysfunction and the promoter methylation of PER1 and CRY1 in patients with cerebral small vessel disease |
| title_full | Relationship between cognitive dysfunction and the promoter methylation of PER1 and CRY1 in patients with cerebral small vessel disease |
| title_fullStr | Relationship between cognitive dysfunction and the promoter methylation of PER1 and CRY1 in patients with cerebral small vessel disease |
| title_full_unstemmed | Relationship between cognitive dysfunction and the promoter methylation of PER1 and CRY1 in patients with cerebral small vessel disease |
| title_short | Relationship between cognitive dysfunction and the promoter methylation of PER1 and CRY1 in patients with cerebral small vessel disease |
| title_sort | relationship between cognitive dysfunction and the promoter methylation of per1 and cry1 in patients with cerebral small vessel disease |
| topic | clock genes PER1 CRY1 methylation cognitive dysfunction cerebral small vessel disease |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2023.1174541/full |
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