Epigenetic mechanisms and the development of asthma

Yang, Ivana V.; Schwartz, David A.

doi:10.1016/j.jaci.2012.07.052

Cited by 118 publications

(86 citation statements)

References 150 publications

(167 reference statements)

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“…These miRNA have been shown to be involved in other biological responses including: tumorigenesis, epigenetic modification, embryonic development, skeletal metabolism, panic disorders, and cardiomyocyte hypertrophy (miR-22); cancer cell proliferation (miR-210) (Xiong, 2012); lipid metabolism (miR-27b) (Vickers et al, 2013); and gastic and colorectal cancers (mi-301a) (Liu et al, 2013;Wang et al, 2013). Yang & Schwartz (2012) recently reported regulation of transcription factors involved in T-cell differentiation and the development of asthma by epigenetic mechanisms including miRNA. In the present study, the target analysis conducted on the identified miRNA suggests numerous targets ranging from transcription factors to cytokines and their receptors with the potential for interaction among these factors.…”

Section: Discussionmentioning

confidence: 99%

Expression kinetics of miRNA involved in dermal toluene 2,4-diisocyanate sensitization

Anderson

Beezhold

Lukomska

et al. 2013

Journal of Immunotoxicology

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Allergic disease is an important occupational health concern, with work-related asthma and allergic contact dermatitis being the most frequently diagnosed occupational illnesses. Diisocyanates, particularly toluene 2,4-diisocyanate (TDI), have been the leading cause of occupational asthma for many years. Understanding the mechanisms behind allergic disease is critical for treatment and prevention. Recently, the study of post-transcriptional regulation by microRNAs (miRNA) has shed light on mechanisms of allergic disease. The present studies report the expression of miRNA during the sensitization phase of an allergic response to TDI in a murine model. Female BALB/c mice were dermally exposed to TDI (0.1-15% [v/v]) or vehicle. RNA was isolated from superficial parotid lymph nodes at timepoints between 1 h and 15 days post-exposure and then miRNA expression was analyzed using array and real-time quantitative PCR analysis. Consistent changes in miRNA expression were identified for miR-21, miR-22, miR-27b, miR-31, miR-126, miR-155, miR-210, and miR-301a. Following TDI exposure, peak expression was observed by Day 4 for the majority of miRNA evaluated with trends in expression correlated to exposure concentration. Confirmed and predicted targets were identified using Diana-microT, miRanda, miRwalk, and Targetscan algorithms. Evaluation of mRNA expression of cytokine and transcription factor targets suggests that miRNA may have a central role early in TDI sensitization. Understanding the role of these miRNA and their specific mechanism of action in sensitization to TDI may provide pertinent information for the identification of other chemical sensitizers while also contributing to the treatment and prevention of allergic disease.

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Section: Discussionmentioning

confidence: 99%

Expression kinetics of miRNA involved in dermal toluene 2,4-diisocyanate sensitization

Anderson

Beezhold

Lukomska

et al. 2013

Journal of Immunotoxicology

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“…As asthma development and progression are affected by environmental factors, a hypothesised role for epigenetic mechanisms has been proposed [7][8][9]. There has been particular interest in a role for DNA methylation, one of the most widely studied epigenetic mechanisms which is known to be responsive to environmental exposures [10].…”

Section: Introductionmentioning

confidence: 99%

Epigenome-wide association study of asthma and wheeze in childhood and adolescence

et al. 2017

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Background: Asthma heritability has only been partially explained by genetic variants and is known to be sensitive to environmental factors, implicating epigenetic modifications such as DNA methylation in its pathogenesis. Methods: Using data collected in the Avon Longitudinal Study of Parents and Children (ALSPAC), we assessed associations of asthma and wheeze with DNA methylation at 7.5 and 16.5 years, at over 450,000 CpG sites in DNA from the peripheral blood of approx. 1000 participants. We used Mendelian randomization (MR), a method of causal inference that uses genetic variants as instrumental variables, to infer the direction of association between DNA methylation and asthma. Results: We identified 302 CpGs associated with current asthma status (FDR-adjusted P value < 0.05) and 445 with current wheeze status at 7.5 years, with substantial overlap between the two. Genes annotated to the 302 associated CpGs were enriched for pathways related to movement of cellular/subcellular components, locomotion, interleukin-4 production and eosinophil migration. All associations attenuated when adjusted for eosinophil and neutrophil cell count estimates. At 16.5 years, two sites were associated with current asthma after adjustment for cell counts. The CpGs mapped to the AP2A2 and IL5RA genes, with a − 2.32 [95% CI − 1.47, − 3.18] and − 2.49 [95% CI − 1.56, − 3.43] difference in percentage methylation in asthma cases respectively. Two-sample bi-directional MR indicated a causal effect of asthma on DNA methylation at several CpG sites at 7. 5 years. However, associations did not persist after adjustment for multiple testing. There was no evidence of a causal effect of asthma on DNA methylation at either of the two CpG sites at 16.5 years. Conclusion: The majority of observed associations are driven by higher eosinophil cell counts in asthma cases, acting as an intermediate phenotype, with important implications for future studies of DNA methylation in atopic diseases.

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“…As noted in recent reviews [8][9][10], our understanding of the role of epigenetic mechanisms in asthma has evolved over the last few years, but only incrementally -in part because much of the work has relied on pre-existing cross-sectional studies that can only explore relationships with concurrent disease, in part because of limitations in the assessment technologies and sources of tissue (typically, unfractionated peripheral blood). However, experimental platforms have now improved and novel models are being proposed.…”

Section: Introductionmentioning

confidence: 99%

The Neonatal Methylome as a Gatekeeper in the Trajectory to Childhood Asthma

DeVries

Vercelli

2017

Epigenomics

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Asthma is a heterogeneous group of conditions that typically begin in early life and result in recurrent, reversible bronchial obstruction. The role played by epigenetic mechanisms in the pathogenesis of childhood asthma is understood only in part. Here we discuss asthma epigenetics within a developmental perspective based on our recent demonstration that the epigenetic trajectory to childhood asthma begins at birth. We next discuss how this trajectory may be affected by prenatal environmental exposures. Finally, we examine in vitro studies that model the impact of asthma-associated exposures on the epigenome. All of these studies specifically surveyed human DNA methylation and involved a genome-wide component. In combination, their results broaden our understanding of asthma pathogenesis and the role the methylome plays in this process.

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Epigenetic mechanisms and the development of asthma

Cited by 118 publications

References 150 publications

Expression kinetics of miRNA involved in dermal toluene 2,4-diisocyanate sensitization

Expression kinetics of miRNA involved in dermal toluene 2,4-diisocyanate sensitization

Epigenome-wide association study of asthma and wheeze in childhood and adolescence

The Neonatal Methylome as a Gatekeeper in the Trajectory to Childhood Asthma

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