Genomics and the respiratory effects of air pollution exposure

Authors

  • JOHN W. HOLLOWAY,

    Corresponding author
    1. Human Development and Health
    2. Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
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  • SANTIYAGU SAVARIMUTHU FRANCIS,

    1. Department of Thoracic Medicine, The Prince Charles Hospital
    2. UQ Thoracic Research Centre, School of Medicine, The University of Queensland, Brisbane, Queensland, Australia
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  • KWUN M. FONG,

    1. Department of Thoracic Medicine, The Prince Charles Hospital
    2. UQ Thoracic Research Centre, School of Medicine, The University of Queensland, Brisbane, Queensland, Australia
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  • IAN A. YANG

    1. Department of Thoracic Medicine, The Prince Charles Hospital
    2. UQ Thoracic Research Centre, School of Medicine, The University of Queensland, Brisbane, Queensland, Australia
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  • The Authors: Professor John Holloway (BSc, PhD), Professor of Allergy and Respiratory Genetics, University of Southampton, leads a research program of medical genomics in allergic diseases, especially asthma. Ms. Santiyagu Savarimuthu Francis (MSc) is a PhD student in the University of Queensland (UQ) Thoracic Research Centre at The Prince Charles Hospital, and is studying the molecular mechanisms involved in progression of chronic obstructive pulmonary disease (COPD). Professor Kwun Fong (MBBS, FRACP, PhD), Thoracic Physician, The Prince Charles Hospital and Director, UQ Thoracic Research Centre, leads a multidisciplinary research team studying lung cancer and airways disease. Associate Professor Ian Yang (MBBS (Hons), PhD, FRACP, Grad Dip Clin Epid), Thoracic Physician, The Prince Charles Hospital and Head of the UQ Northside Clinical School, has research interests in COPD, asthma and air pollution.

  • SERIES EDITORS: IAN YANG AND STEPHEN HOLGATE

John W. Holloway, Human Genetics and Medical Genomics, University of Southampton Faculty of Medicine, Duthie Building, MP808, Southampton General Hospital, Southampton SO16 6YD, UK. Email: j.w.holloway@soton.ac.uk

ABSTRACT

Adverse health effects from air pollutants remain important, despite improvement in air quality in the past few decades. The exact mechanisms of lung injury from exposure to air pollutants are not yet fully understood. Studying the genome (e.g. single-nucleotide polymorphisms (SNP) ), epigenome (e.g. methylation of genes), transcriptome (mRNA expression) and microRNAome (microRNA expression) has the potential to improve our understanding of the adverse effects of air pollutants. Genome-wide association studies of SNP have detected SNP associated with respiratory phenotypes; however, to date, only candidate gene studies of air pollution exposure have been performed. Changes in epigenetic processes, such DNA methylation that leads to gene silencing without altering the DNA sequence, occur with air pollutant exposure, especially global and gene-specific methylation changes. Respiratory cell line and animal models demonstrate distinct gene expression signatures in the transcriptome, arising from exposure to particulate matter or ozone. Particulate matter and other environmental toxins alter expression of microRNA, which are short non-coding RNA that regulate gene expression. While it is clearly important to contain rising levels of air pollution, strategies also need to be developed to minimize the damaging effects of air pollutant exposure on the lung, especially for patients with chronic lung disease and for people at risk of future lung disease. Careful study of genomic responses will improve our understanding of mechanisms of lung injury from air pollution and enable future clinical testing of interventions against the toxic effects of air pollutants.

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