Genome-wide DNA methylation analysis in permanent atrial fibrillation

Zhao, Guochang; Zhou, Jian; Gao, Jie; Liu, Yan; Gu, Song; Zhang, Xitao; Su, Pixiong

doi:10.3892/mmr.2017.7221

Cited by 28 publications

(25 citation statements)

References 52 publications

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“…46 Several studies have suggested that AF is associated with methylation of genetic loci related to AF susceptibility. 47,48 Although any relationship between choline metabolism and methylation specifically in the myocardium is elusive, it is possible that the present findings reflect methylation status and epigenetic regulation relevant to AF development and persistence.…”

Section: Possible Mechanismsmentioning

confidence: 88%

Plasma Concentrations and Dietary Intakes of Choline and Betaine in Association With Atrial Fibrillation Risk: Results From 3 Prospective Cohorts With Different Health Profiles

Zuo

Svingen

Tell

et al. 2018

JAHA

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BackgroundAlthough choline metabolism has been associated with atherosclerotic heart disease, less research attention has been paid to the associations of choline and its oxidative metabolite betaine with cardiac arrhythmias.Methods and ResultsWe evaluated associations of plasma concentrations and dietary intakes of choline and betaine with long‐term atrial fibrillation (AF) risk in a community‐based cohort, HUSK ([the Hordaland Health Study] n=6949), and validated the findings in 2 patient cohorts: the Western Norway Coronary Angiography Cohort (n=4164) and the NORVIT (Norwegian B‐Vitamin) Trial (n=3733). Information on AF was obtained from the CVDNOR (Cardiovascular Disease in Norway) project. In HUSK, WECAC (Western Norway Coronary Angiography Cohort), and NORVIT, 552, 411, and 663 AF cases were identified during a median follow‐up time of 10.9, 7.3, and, 8.7 years, respectively. Plasma concentrations of choline and betaine were significantly positively associated with later AF risk after multivariable adjustments in HUSK. Such associations were independently replicated in the 2 external prospective patient cohorts. The pooled hazard ratio was 1.13 (95% confidence interval 1.08‐1.19, P<0.001) and 1.16 (95% confidence interval 1.10‐1.22, P<0.001) per SD increment for log‐transformed choline and betaine, respectively. Moreover, dietary intake of choline was marginally associated with AF risk (pooled hazard ratio 1.29, 95% confidence interval 1.01‐1.66, fifth versus first quintile), whereas no significant association was observed between dietary betaine and AF risk.ConclusionsOur findings indicate that plasma concentrations as well as dietary intake of choline, but not betaine, are associated with subsequent risk of AF, suggesting a potential role of choline metabolism in the pathogenesis of AF.Clinical Trial RegistrationURL: https://www.clinicaltrials.gov.Unique identifier: NCT00671346.

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Section: Possible Mechanismsmentioning

confidence: 88%

Plasma Concentrations and Dietary Intakes of Choline and Betaine in Association With Atrial Fibrillation Risk: Results From 3 Prospective Cohorts With Different Health Profiles

Zuo

Svingen

Tell

et al. 2018

JAHA

View full text Add to dashboard Cite

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“…DNA methylation, a pre-transcriptional modification characterized by the addition of methyl groups to specific nucleotides, regulates the stability of gene expression states and maintains genome integrity by collaborating with proteins that modify nucleosomes (Ma et al, 2014;Tao et al, 2016;Shen et al, 2017). Previous studies considered that changes in DNA methylation states contribute to the regulation of biological processes underlying AF, such as fibrosis, atrial dilatation, atrial fibroblast proliferation and differentiation from fibroblasts into myofibroblasts (Zhao et al, 2017). To further enhance the biological understanding of the atrial fibrillation, our study focused on DNA methylation, particularly with respect to how it relates to mRNA expression.…”

Section: Discussionmentioning

confidence: 99%

The Joint Analysis of Multi-Omics Data Revealed the Methylation-Expression Regulations in Atrial Fibrillation

Liu

Shi

Ding

et al. 2020

Front. Bioeng. Biotechnol.

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Atrial fibrillation (AF) is one of the most prevalent heart rhythm disorder. The causes of AF include age, male sex, diabetes, hypertension, valve disease, and systolic/diastolic dysfunction. But on molecular level, its mechanisms are largely unknown. In this study, we collected 10 patients with persistent atrial fibrillation, 10 patients with paroxymal atrial fibrillation and 10 healthy individuals and did Methylation EPICBead Chip and RNA sequencing. By analyzing the methylation and gene expression data using machine learning based feature selection method Boruta, we identified the key genes that were strongly associated with AF and found their interconnections. The results suggested that the methylation of KIF15 may regulate the expression of PSMC3, TINAG, and NUDT6. The identified AF associated methylation-expression regulations may help understand the molecular mechanisms of AF from a multi-omics perspective.

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“…However, there are only a few researches involved in the regulation mechanism of ITGB4 expression. ITGB4 proximal promoter and the first exon have a high GC content, 39 and it was illustrated that ITGB4 expression in breast epithelial cells is regulated by complex epigenetic modifications 20,40 . Epigenetic modification, such as DNA methylation, histone modification and non‐coding RNA, involves alterations of genome information and interpretation, without alterations of nucleotide sequence.…”

Section: Discussionmentioning

confidence: 99%

DNA methylation down‐regulates integrin β4 expression in asthmatic airway epithelial cells

Yang

Lin

et al. 2020

Clin Experimental Allergy

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Background: Integrin β4 (ITGB4) is a hemi-desmosome protein which is downregulated in the airway epithelial cells of asthma patients. The proximal promoters and exons of ITGB4 contain CpG islands or multiple CpG sites both in human and mice, which indicated the possible methylation regulation of ITGB4 in airway epithelial cells. Objective: We sought to unveil that DNA methylation regulates the decreased ITGB4 during the pathogenesis of asthma. Methods: Mice were exposed to house dust mite (HDM) extracts to construct an asthma model. 5-Aza-2'-deoxycytidine (5-AZA) or dexamethasone (DEX) were added in the last two weeks. Besides, the primary human bronchial epithelial (HBE) cells were incubated for the detection of ITGB4 expression and methylation status after HDM stress. Furthermore, DNA methylation of ITGB4 in peripheral blood was measured in asthma patients. Logistic regression was employed to evaluate the association between methylation sites and asthma patients' ages in the control of potential confounders. Moreover, the correlations between differentially methylated sites (DMSs) and clinical parameters in asthma patients were assessed. Finally, the ability of candidate DMSs to predict asthma was evaluated by receiver operating characteristic (ROC) analysis and principal component analysis (PCA). Results: We found that in HDM-stressed asthma model, DNA methylation regulated the reduced ITGB4 expression in airway epithelial cells. Moreover, alteration in the specific CpG sites (chr17:73717720 and chr17:73717636) of ITGB4 may regulate ITGB4 expression and further may be associated with the clinically phenotypic of asthma. The specific DMSs of ITGB4 in peripheral blood can distinguish asthma patients from healthy controls (HCs) effectively. Conclusions and Clinical Relevance: This study confirmed that DNA methylation regulates the decreased expression of ITGB4 in the airway epithelial cells of asthma patients. These results supply some useful insights to the mechanism of the decreased ITGB4 in asthmatic airway epithelial and provide possible targets for early prediction and screening of asthma.

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Genome-wide DNA methylation analysis in permanent atrial fibrillation

Cited by 28 publications

References 52 publications

Plasma Concentrations and Dietary Intakes of Choline and Betaine in Association With Atrial Fibrillation Risk: Results From 3 Prospective Cohorts With Different Health Profiles

Plasma Concentrations and Dietary Intakes of Choline and Betaine in Association With Atrial Fibrillation Risk: Results From 3 Prospective Cohorts With Different Health Profiles

The Joint Analysis of Multi-Omics Data Revealed the Methylation-Expression Regulations in Atrial Fibrillation

DNA methylation down‐regulates integrin β4 expression in asthmatic airway epithelial cells

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