title: The genetic and epigenetic landscapes of the epithelium in asthma.
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.
authors.affiliation: School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, HMRI building, The University of Newcastle, Callaghan, NSW, 2308, Australia. fatemeh.moheimani@newcastle.edu.au.|Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, The University of Newcastle, New South Wales, Australia. fatemeh.moheimani@newcastle.edu.au.
authors.forename: Fatemeh
authors.identifier: http://orcid.org/0000-0003-1239-3887
authors.initials: F
authors.lastname: Moheimani
authors.affiliation: School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, HMRI building, The University of Newcastle, Callaghan, NSW, 2308, Australia.|Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, The University of Newcastle, New South Wales, Australia.
authors.forename: Alan C-Y
authors.initials: AC
authors.lastname: Hsu
authors.affiliation: School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, HMRI building, The University of Newcastle, Callaghan, NSW, 2308, Australia.|Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, The University of Newcastle, New South Wales, Australia.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Reid
authors.affiliation: School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, HMRI building, The University of Newcastle, Callaghan, NSW, 2308, Australia.|Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, The University of Newcastle, New South Wales, Australia.|Department of Biochemistry and Microbiology, University of Victoria, Victoria, Canada.
authors.forename: Teresa
authors.initials: T
authors.lastname: Williams
authors.affiliation: Telethon Kids Institute, Centre for Health Research, The University of Western Australia, Nedlands, 6009, Western Australia, Australia.|Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, 6001, Western Australia, Australia.|School of Paediatrics and Child Health, The University of Western Australia, Nedlands, 6009, Western Australia, Australia.|Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, The University of Western Australia, Nedlands, 6009, Western Australia, Australia.
authors.forename: Anthony
authors.initials: A
authors.lastname: Kicic
authors.affiliation: Telethon Kids Institute, Centre for Health Research, The University of Western Australia, Nedlands, 6009, Western Australia, Australia.|Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, 6001, Western Australia, Australia.|School of Paediatrics and Child Health, The University of Western Australia, Nedlands, 6009, Western Australia, Australia.|Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, The University of Western Australia, Nedlands, 6009, Western Australia, Australia.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Stick
authors.affiliation: School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, HMRI building, The University of Newcastle, Callaghan, NSW, 2308, Australia.|Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, The University of Newcastle, New South Wales, Australia.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Hansbro
authors.affiliation: Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, The University of Newcastle, New South Wales, Australia.|Department of Respiratory and Sleep Medicine, John Hunter Hospital, New South Wales, Australia.
authors.forename: Peter A B
authors.initials: PA
authors.lastname: Wark
authors.affiliation: School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, HMRI building, The University of Newcastle, Callaghan, NSW, 2308, Australia.|Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, The University of Newcastle, New South Wales, Australia.|Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, Canada.
authors.forename: Darryl A
authors.initials: DA
authors.lastname: Knight
keywords: Asthma; DNA methylation; Epithelial cells; Genes; Histone acetylation; microRNA