Characteristic DNA methylation profiles in peripheral blood monocytes are associated with inflammatory phenotypes of asthma

Gunawardhana, Lakshitha; Gibson, Peter G.; Simpson, Jodie L.; Benton, Miles C.; Lea, Rodney Arthur; Baines, Katherine J.

doi:10.4161/epi.33066

Cited by 59 publications

(42 citation statements)

References 52 publications

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“…The current findings will be particularly useful for those seeking a better understanding of the relationship between smoking and illnesses not classically associated with inflammation. The prominence of inflammatory related genes reported in prior analyses of the effects of smoking on DNA methylation from infants and adults has clearly outlined a plausible molecular explanation for the relationship of smoking to the increased rates of asthma and respiratory tract infections observed in infants and adults (Dogan et al, ; Gunawardhana et al, ; Zhang, Yang, Burwinkel, Breitling, & Brenner, ). However, these more limited prior findings do not readily explain a connection between smoking and syndromes such as mild intellectual delay or attention deficit hyperactivity disorder in the offspring of mothers who smoke (DiFranza, Aligne, & Weitzman, ; Langley, Rice, Van den Bree, & Thapar, ; Mick, Biederman, Faraone, Sayer, & Kleinman, ; Milberger, Biederman, Faraone, Chen, & Jones, ) or the increased risk for later onset neuropsychiatric disorders, namely, panic disorder, and schizophrenia in adults who smoke (Gurillo, Jauhar, Murray, & MacCabe, ; Kendler et al, ).…”

Section: Discussionmentioning

confidence: 99%

Genetically contextual effects of smoking on genome wide DNA methylation

Dogan

Beach

Philibert

2017

American J of Med Genetics Pt B

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Smoking is the leading cause of death in the United States. It exerts its effects by increasing susceptibility to a variety of complex disorders among those who smoke, and if pregnant, to their unborn children. In prior efforts to understand the epigenetic mechanisms through which this increased vulnerability is conveyed, a number of investigators have conducted genome wide methylation analyses. Unfortunately, secondary to methodological limitations, these studies were unable to examine methylation in gene regions with significant amounts of genetic variation. Using genome wide genetic and epigenetic data from the Framingham Heart Study, we re-examined the relationship of smoking status to genome wide methylation status. When only methylation status is considered, smoking was significantly associated with differential methylation in 310 genes that map to a variety of biological process and cellular differentiation pathways. However, when SNP effects on the magnitude of smoking associated methylation changes are also considered, cis and trans-interaction effects were noted at a total of 266 and 4353 genes with no marked enrichment for any biological pathways. Furthermore, the SNP variation participating in the significant interaction effects is enriched for loci previously associated with complex medical illnesses. The enlarged scope of the methylome shown to be affected by smoking may better explicate the mediational pathways linking smoking with a myriad of smoking related complex syndromes. Additionally, these results strongly suggest that combined epigenetic and genetic data analyses may be critical for a more complete understanding of the relationship between environmental variables, such as smoking, and pathophysiological outcomes.

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Section: Discussionmentioning

confidence: 99%

Genetically contextual effects of smoking on genome wide DNA methylation

Dogan

Beach

Philibert

2017

American J of Med Genetics Pt B

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“…Prospective examination of methylation patterns in newborns in relation to asthma development might identify genes and mechanisms involved in the developmental origins of asthma. 5 Epigenome-wide association studies (EWASs) of DNA methylation in blood in relation to asthma (numbers of cases range from [6][7][8][9][10][11][12] have identified differential methylation at some specific gene regions. The only meta-analysis of epigenome-wide methylation in childhood asthma included 392 cases but did not examine newborn methylation.…”

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confidence: 99%

Epigenome-wide meta-analysis of DNA methylation and childhood asthma

Reese¹,

Xu²,

Dekker³

et al. 2019

Journal of Allergy and Clinical Immunology

156

188

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Background: Epigenetic mechanisms, including methylation, can contribute to childhood asthma. Identifying DNA methylation profiles in asthmatic patients can inform disease pathogenesis. Objective: We sought to identify differential DNA methylation in newborns and children related to childhood asthma. Methods: Within the Pregnancy And Childhood Epigenetics consortium, we performed epigenome-wide meta-analyses of school-age asthma in relation to CpG methylation (Illumina450K) in blood measured either in newborns, in prospective analyses, or cross-sectionally in school-aged children. We also identified differentially methylated regions. Results: In newborns (8 cohorts, 668 cases), 9 CpGs (and 35 regions) were differentially methylated (epigenome-wide significance, false discovery rate < 0.05) in relation to asthma development. In a cross-sectional meta-analysis of asthma and methylation in children (9 cohorts, 631 cases), we identified 179 CpGs (false discovery rate < 0.05) and 36 differentially methylated regions. In replication studies of methylation in other tissues, most of the 179 CpGs discovered in blood replicated, despite smaller sample sizes, in studies of nasal respiratory epithelium or eosinophils. Pathway analyses highlighted enrichment for asthma-relevant immune processes and overlap in pathways enriched both in newborns and children. Gene expression correlated with methylation at most loci. Functional annotation supports a regulatory effect on gene expression at many asthma-associated CpGs. Several implicated genes are targets for approved or experimental drugs, including IL5RA and KCNH2. Conclusion: Novel loci differentially methylated in newborns represent potential biomarkers of risk of asthma by school age. Cross-sectional associations in children can reflect both risk for and effects of disease. Asthma-related differential methylation in blood in children was substantially replicated in eosinophils and respiratory epithelium. (J Allergy Clin Immunol 2019;143:2062-74.)

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“…It is reported that increase in the local concentration of inflammatory neuropeptides may stimulate bronchial fibers, which rapidly adapts receptors and provokes the cough reflex 48. The neuroactive ligand–receptor pathway includes many G-protein-coupled receptors, which are often located on the cell surface and involved in the transduction of an endogenous signal into an intracellular response 49. G-protein-coupled receptors regulate vital processes by controlling the expression and function of seven transmembrane receptors, which play a particularly important role in some widespread neurological disorders 19.…”

Section: Resultsmentioning

confidence: 99%

Network pharmacology-based identification of key pharmacological pathways of Yin–Huang–Qing–Fei capsule acting on chronic bronchitis

Yang¹,

Zhang²,

Weiqiong³

et al. 2016

COPD

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For decades in China, the Yin–Huang–Qing–Fei capsule (YHQFC) has been widely used in the treatment of chronic bronchitis, with good curative effects. Owing to the complexity of traditional Chinese herbal formulas, the pharmacological mechanism of YHQFC remains unclear. To address this problem, a network pharmacology-based strategy was proposed in this study. At first, the putative target profile of YHQFC was predicted using MedChem Studio, based on structural and functional similarities of all available YHQFC components to the known drugs obtained from the DrugBank database. Then, an interaction network was constructed using links between putative YHQFC targets and known therapeutic targets of chronic bronchitis. Following the calculation of four topological features (degree, betweenness, closeness, and coreness) of each node in the network, 475 major putative targets of YHQFC and their topological importance were identified. In addition, a pathway enrichment analysis based on the Kyoto Encyclopedia of Genes and Genomes pathway database indicated that the major putative targets of YHQFC are significantly associated with various pathways involved in anti-inflammation processes, immune responses, and pathological changes caused by asthma. More interestingly, eight major putative targets of YHQFC (interleukin [IL]-3, IL-4, IL-5, IL-10, IL-13, FCER1G, CCL11, and EPX) were demonstrated to be associated with the inflammatory process that occurs during the progression of asthma. Finally, a molecular docking simulation was performed and the results exhibited that 17 pairs of chemical components and candidate YHQFC targets involved in asthma pathway had strong binding efficiencies. In conclusion, this network pharmacology-based investigation revealed that YHQFC may attenuate the inflammatory reaction of chronic bronchitis by regulating its candidate targets, which may be implicated in the major pathological processes of the asthma pathway.

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Characteristic DNA methylation profiles in peripheral blood monocytes are associated with inflammatory phenotypes of asthma

Cited by 59 publications

References 52 publications

Genetically contextual effects of smoking on genome wide DNA methylation

Genetically contextual effects of smoking on genome wide DNA methylation

Epigenome-wide meta-analysis of DNA methylation and childhood asthma

Network pharmacology-based identification of key pharmacological pathways of Yin–Huang–Qing–Fei capsule acting on chronic bronchitis

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Characteristic DNA methylation profiles in peripheral blood monocytes are associated with inflammatory phenotypes of asthma

Cited by 59 publications

References 52 publications

Genetically contextual effects of smoking on genome wide DNA methylation

Genetically contextual effects of smoking on genome wide DNA methylation

Epigenome-wide meta-analysis of DNA methylation and childhood asthma

Network pharmacology-based identification of key pharmacological pathways of Yin&ndash;Huang&ndash;Qing&ndash;Fei capsule acting on chronic bronchitis

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Network pharmacology-based identification of key pharmacological pathways of Yin–Huang–Qing–Fei capsule acting on chronic bronchitis