Associations of B‐Type Natriuretic Peptide and Its Coding Gene Promoter Methylation With Functional Outcome of Acute Ischemic Stroke: A Mediation Analysis
Background The prognostic role of B‐type natriuretic peptide (BNP) in stroke has been suggested, but limited studies have shown mixed results and unknown underlying mechanisms. DNA methylation, a molecular modification that alters gene expression, may represent a candidate mechanism for this purpose...
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| Format: | Article |
| Language: | English |
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Wiley
2020-09-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.120.017499 |
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| author | Aili Wang Mingzhi Zhang Yi Ding Xingbo Mo Chongke Zhong Zhengbao Zhu Daoxia Guo Xiaowei Zheng Tan Xu Yan Liu Yonghong Zhang Hao Peng |
| author_facet | Aili Wang Mingzhi Zhang Yi Ding Xingbo Mo Chongke Zhong Zhengbao Zhu Daoxia Guo Xiaowei Zheng Tan Xu Yan Liu Yonghong Zhang Hao Peng |
| author_sort | Aili Wang |
| collection | DOAJ |
| description | Background The prognostic role of B‐type natriuretic peptide (BNP) in stroke has been suggested, but limited studies have shown mixed results and unknown underlying mechanisms. DNA methylation, a molecular modification that alters gene expression, may represent a candidate mechanism for this purpose. We aimed to examine the associations of BNP and methylation of its coding gene (natriuretic peptide B [NPPB]) with the functional outcome in a large sample of patients with acute ischemic stroke from CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). Methods and Results Leveraging participants from CATIS with available specimens, serum proBNP (equimolarly produced with BNP) was measured in 3216 patients (mean age, 62 years; 64% men), and peripheral blood DNA methylation of the NPPB promoter was quantified by targeted bisulfite sequencing in 806 patients (mean age, 62 years; 54% men). The functional outcome was defined as an ordered modified Rankin Scale score assessed at 14 days or hospital discharge after stroke onset. Mediation analysis was conducted to test the potential mediating effect of proBNP on the relationship between NPPB methylation and functional outcome. The results showed that a higher level of proBNP was significantly associated with a higher risk of having a poorer functional outcome (odds ratio [OR], 1.14; P=0.006). Every 5% of hypermethylation at 2 (Chr1:11919160 [OR, 0.93; P=0.022] and Chr1:11918989 [OR, 0.92; P=0.032]) of 11 CpG loci assayed was associated with 7% and 8% lower risk, respectively, of having a poor functional outcome. In addition, proBNP was negatively correlated to hypermethylation at 1 CpG (Chr1:11918989 [β=−0.029; P=0.009]) and mediated approximately 7.69% (95% CI, 2.50%–13.82%) of the association between this CpG methylation and the functional outcome. Conclusions Hypermethylation at the NPPB promoter is associated with the functional outcome after ischemic stroke, at least partially by suppressing BNP expression or excretion. |
| first_indexed | 2024-04-24T15:10:19Z |
| format | Article |
| id | doaj.art-1b9d61f8ff034e3092019d3fd38c085f |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-04-24T15:10:19Z |
| publishDate | 2020-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-1b9d61f8ff034e3092019d3fd38c085f2024-04-02T11:31:39ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802020-09-0191810.1161/JAHA.120.017499Associations of B‐Type Natriuretic Peptide and Its Coding Gene Promoter Methylation With Functional Outcome of Acute Ischemic Stroke: A Mediation AnalysisAili Wang0Mingzhi Zhang1Yi Ding2Xingbo Mo3Chongke Zhong4Zhengbao Zhu5Daoxia Guo6Xiaowei Zheng7Tan Xu8Yan Liu9Yonghong Zhang10Hao Peng11Department of Epidemiology School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases Medical College of Soochow University Suzhou ChinaDepartment of Epidemiology School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases Medical College of Soochow University Suzhou ChinaDepartment of Epidemiology School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases Medical College of Soochow University Suzhou ChinaDepartment of Epidemiology School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases Medical College of Soochow University Suzhou ChinaDepartment of Epidemiology School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases Medical College of Soochow University Suzhou ChinaDepartment of Epidemiology School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases Medical College of Soochow University Suzhou ChinaDepartment of Epidemiology School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases Medical College of Soochow University Suzhou ChinaDepartment of Epidemiology School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases Medical College of Soochow University Suzhou ChinaDepartment of Epidemiology School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases Medical College of Soochow University Suzhou ChinaGenesky Biotechnologies Inc Shanghai ChinaDepartment of Epidemiology School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases Medical College of Soochow University Suzhou ChinaDepartment of Epidemiology School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases Medical College of Soochow University Suzhou ChinaBackground The prognostic role of B‐type natriuretic peptide (BNP) in stroke has been suggested, but limited studies have shown mixed results and unknown underlying mechanisms. DNA methylation, a molecular modification that alters gene expression, may represent a candidate mechanism for this purpose. We aimed to examine the associations of BNP and methylation of its coding gene (natriuretic peptide B [NPPB]) with the functional outcome in a large sample of patients with acute ischemic stroke from CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). Methods and Results Leveraging participants from CATIS with available specimens, serum proBNP (equimolarly produced with BNP) was measured in 3216 patients (mean age, 62 years; 64% men), and peripheral blood DNA methylation of the NPPB promoter was quantified by targeted bisulfite sequencing in 806 patients (mean age, 62 years; 54% men). The functional outcome was defined as an ordered modified Rankin Scale score assessed at 14 days or hospital discharge after stroke onset. Mediation analysis was conducted to test the potential mediating effect of proBNP on the relationship between NPPB methylation and functional outcome. The results showed that a higher level of proBNP was significantly associated with a higher risk of having a poorer functional outcome (odds ratio [OR], 1.14; P=0.006). Every 5% of hypermethylation at 2 (Chr1:11919160 [OR, 0.93; P=0.022] and Chr1:11918989 [OR, 0.92; P=0.032]) of 11 CpG loci assayed was associated with 7% and 8% lower risk, respectively, of having a poor functional outcome. In addition, proBNP was negatively correlated to hypermethylation at 1 CpG (Chr1:11918989 [β=−0.029; P=0.009]) and mediated approximately 7.69% (95% CI, 2.50%–13.82%) of the association between this CpG methylation and the functional outcome. Conclusions Hypermethylation at the NPPB promoter is associated with the functional outcome after ischemic stroke, at least partially by suppressing BNP expression or excretion.https://www.ahajournals.org/doi/10.1161/JAHA.120.017499B‐type natriuretic peptideDNA methylationfunctional outcomeischemic stroke |
| spellingShingle | Aili Wang Mingzhi Zhang Yi Ding Xingbo Mo Chongke Zhong Zhengbao Zhu Daoxia Guo Xiaowei Zheng Tan Xu Yan Liu Yonghong Zhang Hao Peng Associations of B‐Type Natriuretic Peptide and Its Coding Gene Promoter Methylation With Functional Outcome of Acute Ischemic Stroke: A Mediation Analysis Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease B‐type natriuretic peptide DNA methylation functional outcome ischemic stroke |
| title | Associations of B‐Type Natriuretic Peptide and Its Coding Gene Promoter Methylation With Functional Outcome of Acute Ischemic Stroke: A Mediation Analysis |
| title_full | Associations of B‐Type Natriuretic Peptide and Its Coding Gene Promoter Methylation With Functional Outcome of Acute Ischemic Stroke: A Mediation Analysis |
| title_fullStr | Associations of B‐Type Natriuretic Peptide and Its Coding Gene Promoter Methylation With Functional Outcome of Acute Ischemic Stroke: A Mediation Analysis |
| title_full_unstemmed | Associations of B‐Type Natriuretic Peptide and Its Coding Gene Promoter Methylation With Functional Outcome of Acute Ischemic Stroke: A Mediation Analysis |
| title_short | Associations of B‐Type Natriuretic Peptide and Its Coding Gene Promoter Methylation With Functional Outcome of Acute Ischemic Stroke: A Mediation Analysis |
| title_sort | associations of b type natriuretic peptide and its coding gene promoter methylation with functional outcome of acute ischemic stroke a mediation analysis |
| topic | B‐type natriuretic peptide DNA methylation functional outcome ischemic stroke |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.120.017499 |
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