The genetic and epigenetic landscapes of the epithelium in asthma

Fatemeh Moheimani, Alan C.Y. Hsu, Andrew T. Reid, Teresa Williams, Anthony Kicic, Stephen M. Stick, Philip M. Hansbro, Peter A.B. Wark, Darryl A. Knight

Research output: Contribution to journalReview article

17 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number119
JournalRespiratory Research
Volume17
Issue number1
DOIs
Publication statusPublished - 22 Sep 2016

Fingerprint

Epigenomics
Asthma
Epithelium
MicroRNAs
Genes
Histone Code
Epithelial Cells
Untranslated RNA
Genome-Wide Association Study
Genetic Association Studies
DNA Methylation
Methylation
Biomarkers
Genome
Technology
Therapeutics

Cite this

Moheimani, F., Hsu, A. C. Y., Reid, A. T., Williams, T., Kicic, A., Stick, S. M., ... Knight, D. A. (2016). The genetic and epigenetic landscapes of the epithelium in asthma. Respiratory Research, 17(1), [119]. https://doi.org/10.1186/s12931-016-0434-4
Moheimani, Fatemeh ; Hsu, Alan C.Y. ; Reid, Andrew T. ; Williams, Teresa ; Kicic, Anthony ; Stick, Stephen M. ; Hansbro, Philip M. ; Wark, Peter A.B. ; Knight, Darryl A. / The genetic and epigenetic landscapes of the epithelium in asthma. In: Respiratory Research. 2016 ; Vol. 17, No. 1.
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Moheimani, F, Hsu, ACY, Reid, AT, Williams, T, Kicic, A, Stick, SM, Hansbro, PM, Wark, PAB & Knight, DA 2016, 'The genetic and epigenetic landscapes of the epithelium in asthma', Respiratory Research, vol. 17, no. 1, 119. https://doi.org/10.1186/s12931-016-0434-4

The genetic and epigenetic landscapes of the epithelium in asthma. / Moheimani, Fatemeh; Hsu, Alan C.Y.; Reid, Andrew T.; Williams, Teresa; Kicic, Anthony; Stick, Stephen M.; Hansbro, Philip M.; Wark, Peter A.B.; Knight, Darryl A.

In: Respiratory Research, Vol. 17, No. 1, 119, 22.09.2016.

Research output: Contribution to journalReview article

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AU - Hsu, Alan C.Y.

AU - Reid, Andrew T.

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AU - Kicic, Anthony

AU - Stick, Stephen M.

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