<i>ASB1</i> differential methylation in ischaemic cardiomyopathy: relationship with left ventricular performance in end‐stage heart failure patients

Ortega, Ana; Tarazón, Estefanía; Gil-Cayuela, Carolina; Martínez‐Dolz, Luis; Lago, Francisca; González-Juanatey, José Ramón; Sandoval, Juan; Portolés, Manuel; Roselló‐Lletí, Esther; Rivera, Miguel

doi:10.1002/ehf2.12289

Cited by 13 publications

(11 citation statements)

References 24 publications

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“…The ASB10 association is likely specific to populations of European decent, as our AA analyses showed no evidence for association. A recent study of ischemic cardiomyopathy in a Spanish population detected significant differential DNA methylation patterns for another member of the ASB family (ASB1 gene), and further highlighted the potential role of DNA methylation of ASB family members for stroke and cardiovascular phenotypes ( Ortega et al, 2018 ).…”

Section: Discussionmentioning

confidence: 92%

Epigenome-Wide Analyses Identify Two Novel Associations With Recurrent Stroke in the Vitamin Intervention for Stroke Prevention Clinical Trial

et al. 2018

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DNA methylation, a well-characterized epigenetic modification that is influenced by both environment and genetic variation, has previously been implicated in a number of complex diseases, including cardiovascular disease and stroke. The goal of this study was to evaluate epigenome-wide associations with recurrent stroke and the folate one-carbon metabolism-related trait, plasma homocysteine (hcy). Differential methylation analyses were performed on 473,864 autosomal CpG loci, using Illumina HumanMethylation 450K array data in 180 ischemic stroke cases from the Vitamin Intervention for Stroke Prevention (VISP) clinical trial. Linear regression was used to assess associations between number of strokes prior to VISP enrollment and measures of hcy with degree of methylation (β-values), while logistic regression was used to evaluate recurrent stroke status and incident recurrent stroke associations. All regression analyses were stratified by race. Two differentially methylated CpG sites exceeded epigenome-wide significance (p ≤ 1.055 × 10−7) for prior number of strokes (PNS) in European Americans. The top locus, cg22812874, was located in the ankyrin repeat and SOCS box containing 10 gene (ASB10; p = 3.4 × 10−9; β = −0.0308; 95% CI = −0.040, −0.002). Methylation locus cg00340919, located in an intron of the tetratricopeptide repeat domain 37 gene, was also statistically significant (TTC37; p = 8.74 × 10−8; β = −0.0517; 95% CI = −0.069, −0.034). An additional 138 CpG sites met our threshold for suggestive significance (p ≤ 5 × 10−5). We evaluated DNA methylation associated with recurrent stroke and hcy phenotypes across the epigenome. Hypermethylation at two CpG sites located in ASB10 and TTC37 was associated with fewer strokes prior to VISP enrollment. Our findings present a foundation for additional epigenome-wide studies, as well as mechanistic studies into epigenetic marks that influence recurrent stroke risk.

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Section: Discussionmentioning

confidence: 92%

Epigenome-Wide Analyses Identify Two Novel Associations With Recurrent Stroke in the Vitamin Intervention for Stroke Prevention Clinical Trial

et al. 2018

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“…A previous study discovered the abnormal expression of these genes in advanced-stage HF patients. 15 CUX1 plays key roles in tumour differentiation and metastasis. [16][17] Abnormal CUX1 expression is associated with the Ebstein anomaly, which affects cardiomyocytes and myocardium differentiation.…”

Section: Discussionmentioning

confidence: 99%

“…19 In the current study, a PPI network analysis showed that ASB1 was defined as a hub gene and played important roles in PPIs in HF. ASB1 is a member of the ankyrin repeat and SOCS box-containing (ASB) family of proteins (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). The ASB1 gene, located on chromosome 2q37, encodes a protein with 335 amino acids.…”

Section: Discussionmentioning

confidence: 99%

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Identification of vital modules and genes associated with heart failure based on weighted gene coexpression network analysis

Bian

Wang

et al. 2022

ESC Heart Failure

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Aims Heart failure (HF) is a chronic heart disease with a high incidence and mortality. Due to the regulatory complexity of gene coexpression networks, the underlying hub genes regulation in HF remain incompletely appreciated. We aimed to explore potential key modules and genes for HF using weighted gene coexpression network analysis (WGCNA). Methods and resultsThe expression profiles by high throughput sequencing of heart tissues samples from HF and non-HF samples were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between HF and non-HF samples were firstly identified. Then, a coexpression network was constructed to identify key modules and potential hub genes. The biological functions of potential hub genes were analysed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Finally, a protein-protein interaction (PPI) network was constructed using the STRING online tool. A total of 135 DEGs (133 up-regulated and 2 down-regulated DEGs) between HF and non-HF samples were identified in the GSE135055 and GSE123976 datasets. Moreover, a total of 38 modules were screened based on WGCNA in the GSE135055 dataset, and six potential hub genes (UCK2, ASB1, CCNI, CUX1, IRX6, and STX16) were screened from the key module by setting the gene significance over 0.2 and the module membership over 0.8. Furthermore, 78 potential hub genes were obtained by taking the intersection of the 135 DEGs and all genes in the key module, and enrichment analysis revealed that they were mainly involved in the MAPK and PI3K-AKT signalling pathways. Finally, in a PPI network constructed with the 78 potential hub genes, CUX1 and ASB1 were identified as hub genes in HF because they were also identified as potential hub genes in the WGCNA. Conclusions To the best of our knowledge, our study is the first to employ WGCNA to identify the key module and hub genes for HF. Our study identified a module and two genes that might play important roles in HF, which may provide potential biomarkers for the diagnosis of HF and improve our knowledge of the molecular mechanisms underlying HF.

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“…Inflammatory cytokines TNFα and IL-1α can up-regulate ASB10 expression that may be involved in glaucoma pathogenesis (25). The methylation status of the ASB1 gene relates with left ventricular performance in ischemic cardiomyopathy, and the epigenetic modification of the ASB1 gene is involved in anxiety-related immune dysregulation (26,27). Recently, the structure and dynamics of the ASB9-Cul-RING E3 ligase complex were reported (28).…”

Section: Significancementioning

confidence: 99%

An unconventional role of an ASB family protein in NF-κB activation and inflammatory response during microbial infection and colitis

Hou

Jia

Yang

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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Nuclear factor κB (NF-κB)–mediated signaling pathway plays a crucial role in the regulation of inflammatory process, innate and adaptive immune responses. The hyperactivation of inflammatory response causes host cell death, tissue damage, and autoinflammatory disorders, such as sepsis and inflammatory bowel disease. However, how these processes are precisely controlled is still poorly understood. In this study, we demonstrated that ankyrin repeat and suppressor of cytokine signaling box containing 1 (ASB1) is involved in the positive regulation of inflammatory responses by enhancing the stability of TAB2 and its downstream signaling pathways, including NF-κB and mitogen-activated protein kinase pathways. Mechanistically, unlike other members of the ASB family that induce ubiquitination-mediated degradation of their target proteins, ASB1 associates with TAB2 to inhibit K48-linked polyubiquitination and thereby promote the stability of TAB2 upon stimulation of cytokines and lipopolysaccharide (LPS), which indicates that ASB1 plays a noncanonical role to further stabilize the target protein rather than induce its degradation. The deficiency of Asb1 protects mice from Salmonella typhimurium– or LPS-induced septic shock and increases the survival of mice. Moreover, Asb1-deficient mice exhibited less severe colitis and intestinal inflammation induced by dextran sodium sulfate. Given the crucial role of ASB proteins in inflammatory signaling pathways, our study offers insights into the immune regulation in pathogen infection and inflammatory disorders with therapeutic implications.

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ASB1 differential methylation in ischaemic cardiomyopathy: relationship with left ventricular performance in end‐stage heart failure patients

Cited by 13 publications

References 24 publications

Epigenome-Wide Analyses Identify Two Novel Associations With Recurrent Stroke in the Vitamin Intervention for Stroke Prevention Clinical Trial

Epigenome-Wide Analyses Identify Two Novel Associations With Recurrent Stroke in the Vitamin Intervention for Stroke Prevention Clinical Trial

Identification of vital modules and genes associated with heart failure based on weighted gene coexpression network analysis

An unconventional role of an ASB family protein in NF-κB activation and inflammatory response during microbial infection and colitis

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