Associations of NPPA promoter true methylation and hydroxymethylation with ischemic stroke and its functional outcome
Abstract Background Atrial natriuretic peptide (ANP) has been associated with ischemic stroke (IS), but the underlying molecular mechanisms are not clear. The objective of this study was to examine whether DNA methylation and hydroxymethylation in the coding gene of ANP (NPPA) were associated with I...
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BMC
2024-11-01
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| Series: | Epigenetics Communications |
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| Online Access: | https://doi.org/10.1186/s43682-024-00029-5 |
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| author | Jialing Yao Linghua Song Jun Jiang Jianan Zhang Linan Chen Wenxiu Fan Ying Lu Xiaolong Zhang Jiexiang Jing Yibing Jin Mingzhi Zhang Yongang Hao Hao Peng |
| author_facet | Jialing Yao Linghua Song Jun Jiang Jianan Zhang Linan Chen Wenxiu Fan Ying Lu Xiaolong Zhang Jiexiang Jing Yibing Jin Mingzhi Zhang Yongang Hao Hao Peng |
| author_sort | Jialing Yao |
| collection | DOAJ |
| description | Abstract Background Atrial natriuretic peptide (ANP) has been associated with ischemic stroke (IS), but the underlying molecular mechanisms are not clear. The objective of this study was to examine whether DNA methylation and hydroxymethylation in the coding gene of ANP (NPPA) were associated with IS, as well as its functional outcome. Methods and results DNA methylation and hydroxymethylation in NPPA promoter region were quantified by targeted bisulfite sequencing and APOBEC-coupled epigenetic sequencing, respectively, in 615 IS patients and 610 age- and sex-matched healthy controls. True methylation was calculated as the quantified methylation level minus the quantified hydroxymethylation level. The functional outcome of IS was evaluated by the modified Rankin Scale (mRS) at a 3-month follow-up visit after onset. Multiple testing was controlled by the false discovery rate approach. Of the nine CpG sites assayed, hypomethylation at eight CpGs was not only associated with an increased risk of having IS but also predicted a higher mRS score after onset (all q < 0.05) and hydroxymethylation at one CpG located at Chr1:11908348 was positively associated with IS (OR = 1.39, 95%CI:1.15–1.68, q < 0.05), after adjusting for covariates and multiple testing. While, hydroxymethylation levels at none of the CpGs assayed were significantly associated with the mRS score. Conclusions DNA methylation and hydroxymethylation in NPPA promoter were associated with the risk of IS and its functional outcome in Chinese adults. |
| format | Article |
| id | doaj-art-fd73b07518bf48c0accaca9a0eed386f |
| institution | Kabale University |
| issn | 2730-7034 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Epigenetics Communications |
| spelling | doaj-art-fd73b07518bf48c0accaca9a0eed386f2024-11-17T12:11:47ZengBMCEpigenetics Communications2730-70342024-11-014111210.1186/s43682-024-00029-5Associations of NPPA promoter true methylation and hydroxymethylation with ischemic stroke and its functional outcomeJialing Yao0Linghua Song1Jun Jiang2Jianan Zhang3Linan Chen4Wenxiu Fan5Ying Lu6Xiaolong Zhang7Jiexiang Jing8Yibing Jin9Mingzhi Zhang10Yongang Hao11Hao Peng12Department of Medical Insurance Price, Suzhou Ninth Hospital affiliated to Soochow UniversityDepartment of Neurology, Dushu Lake Affiliated Hospital of Soochow UniversityDepartment of Tuberculosis Control, Suzhou Center for Disease Control and PreventionDepartment of Chronic Disease, Taicang Center for Disease Control and PreventionDepartment of Epidemiology, School of Public Health, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow UniversityDepartment of Epidemiology, School of Public Health, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow UniversityDepartment of Epidemiology, School of Public Health, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow UniversityDepartment of Tuberculosis Control, Suzhou Center for Disease Control and PreventionDepartment of Epidemiology, School of Public Health, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow UniversityDepartment of Epidemiology, School of Public Health, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow UniversityDepartment of Epidemiology, School of Public Health, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow UniversityDepartment of Neurology, Dushu Lake Affiliated Hospital of Soochow UniversityDepartment of Epidemiology, School of Public Health, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow UniversityAbstract Background Atrial natriuretic peptide (ANP) has been associated with ischemic stroke (IS), but the underlying molecular mechanisms are not clear. The objective of this study was to examine whether DNA methylation and hydroxymethylation in the coding gene of ANP (NPPA) were associated with IS, as well as its functional outcome. Methods and results DNA methylation and hydroxymethylation in NPPA promoter region were quantified by targeted bisulfite sequencing and APOBEC-coupled epigenetic sequencing, respectively, in 615 IS patients and 610 age- and sex-matched healthy controls. True methylation was calculated as the quantified methylation level minus the quantified hydroxymethylation level. The functional outcome of IS was evaluated by the modified Rankin Scale (mRS) at a 3-month follow-up visit after onset. Multiple testing was controlled by the false discovery rate approach. Of the nine CpG sites assayed, hypomethylation at eight CpGs was not only associated with an increased risk of having IS but also predicted a higher mRS score after onset (all q < 0.05) and hydroxymethylation at one CpG located at Chr1:11908348 was positively associated with IS (OR = 1.39, 95%CI:1.15–1.68, q < 0.05), after adjusting for covariates and multiple testing. While, hydroxymethylation levels at none of the CpGs assayed were significantly associated with the mRS score. Conclusions DNA methylation and hydroxymethylation in NPPA promoter were associated with the risk of IS and its functional outcome in Chinese adults.https://doi.org/10.1186/s43682-024-00029-5Atrial natriuretic peptideDNA methylationDNA hydroxymethylationIschemic stroke |
| spellingShingle | Jialing Yao Linghua Song Jun Jiang Jianan Zhang Linan Chen Wenxiu Fan Ying Lu Xiaolong Zhang Jiexiang Jing Yibing Jin Mingzhi Zhang Yongang Hao Hao Peng Associations of NPPA promoter true methylation and hydroxymethylation with ischemic stroke and its functional outcome Epigenetics Communications Atrial natriuretic peptide DNA methylation DNA hydroxymethylation Ischemic stroke |
| title | Associations of NPPA promoter true methylation and hydroxymethylation with ischemic stroke and its functional outcome |
| title_full | Associations of NPPA promoter true methylation and hydroxymethylation with ischemic stroke and its functional outcome |
| title_fullStr | Associations of NPPA promoter true methylation and hydroxymethylation with ischemic stroke and its functional outcome |
| title_full_unstemmed | Associations of NPPA promoter true methylation and hydroxymethylation with ischemic stroke and its functional outcome |
| title_short | Associations of NPPA promoter true methylation and hydroxymethylation with ischemic stroke and its functional outcome |
| title_sort | associations of nppa promoter true methylation and hydroxymethylation with ischemic stroke and its functional outcome |
| topic | Atrial natriuretic peptide DNA methylation DNA hydroxymethylation Ischemic stroke |
| url | https://doi.org/10.1186/s43682-024-00029-5 |
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