- Title
- The genetic and epigenetic landscapes of the epithelium in asthma
- Creator
- Moheimani, Fatemeh; Hsu, Alan C-Y.; Reid, Aandrew T.; Williams, Teresa; Kicic, Anthony; Stick, Stephen M.; Hansbro, Philip M.; Wark, Peter A. B.; Knight, Darryl A.
- Relation
- NHMRC.1064405 http://purl.org/au-research/grants/nhmrc/1064405
- Relation
- Respiratory Research Vol. 17, Issue 199
- Publisher Link
- http://dx.doi.org/10.1186/s12931-016-0434-4
- Publisher
- BioMed Central
- Resource Type
- journal article
- Date
- 2016
- Description
- Asthma is a global health problem with increasing prevalence. The airway epithelium is the initial barrier against inhaled noxious agents or aeroallergens. In asthma, the airway epithelium suffers from structural and functional abnormalities and as such, is more susceptible to normally innocuous environmental stimuli. The epithelial structural and functional impairments are now recognised as a significant contributing factor to asthma pathogenesis. Both genetic and environmental risk factors play important roles in the development of asthma with an increasing number of genes associated with asthma susceptibility being expressed in airway epithelium. Epigenetic factors that regulate airway epithelial structure and function are also an attractive area for assessment of susceptibility to asthma. In this review we provide a comprehensive discussion on genetic factors; from using linkage designs and candidate gene association studies to genome-wide association studies and whole genome sequencing, and epigenetic factors; DNA methylation, histone modifications, and non-coding RNAs (especially microRNAs), in airway epithelial cells that are functionally associated with asthma pathogenesis. Our aims were to introduce potential predictors or therapeutic targets for asthma in airway epithelium. Overall, we found very small overlap in asthma susceptibility genes identified with different technologies. Some potential biomarkers are IRAKM, PCDH1, ORMDL3/GSDMB, IL-33, CDHR3 and CST1 in airway epithelial cells. Recent studies on epigenetic regulatory factors have further provided novel insights to the field, particularly their effect on regulation of some of the asthma susceptibility genes (e.g. methylation of ADAM33). Among the epigenetic regulatory mechanisms, microRNA networks have been shown to regulate a major portion of post-transcriptional gene regulation. Particularly, miR-19a may have some therapeutic potential.
- Subject
- epithelial cells; asthma; Genes; DNA methylation; histone acetylation; microRNA
- Identifier
- http://hdl.handle.net/1959.13/1344623
- Identifier
- uon:29462
- Identifier
- ISSN:1465-993X
- Rights
- This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Language
- eng
- Full Text
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