“Environmental transmission factors and host genetic polymorphisms influencing NTM infection in patients with no overt immunodeficiency”

Halstrom, Samuel (2017). “Environmental transmission factors and host genetic polymorphisms influencing NTM infection in patients with no overt immunodeficiency” MPhil Thesis, School of Medicine, The University of Queensland. doi:10.14264/uql.2017.793

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Author Halstrom, Samuel
Thesis Title “Environmental transmission factors and host genetic polymorphisms influencing NTM infection in patients with no overt immunodeficiency”
School, Centre or Institute School of Medicine
Institution The University of Queensland
DOI 10.14264/uql.2017.793
Publication date 2017-06-02
Thesis type MPhil Thesis
Supervisor Rachel Thomson
Patricia Price
John Miles
Total pages 83
Language eng
Subjects 0604 Genetics
1108 Medical Microbiology
1107 Immunology
Formatted abstract
Pulmonary disease associated with non-tuberculous mycobacteria (NTM) is a poorly understood and difficult to treat condition. It is an increasingly common problem in a subset of older individuals, with NTM lung disease now reported more frequently than tuberculosis in Australia. Environmental exposure appears to be the primary route for pulmonary NTM infection, but specific risk factors remain poorly determined. A large subset of patients with pulmonary NTM disease appears to be immunocompetent, but the existence of an as yet unidentified deficiency in these patients’ immune response to NTM infection may influence their risk of infection.

This thesis begins with a review of the evidence that pathogenic species of NTM have been isolated from drinking water distribution systems, soil and house dust, so exposure may be very common. A defect in immune response appears critical to the development of disease. Ways by which genetic make-up may predispose some individuals to pulmonary NTM disease were addressed. This involved investigations of polymorphic alleles across IL10 and a group of three novel genes P2X4R, P2X7R and CAMKK2.

DNA was obtained from 124 patients with pulmonary NTM disease attending Greenslopes Private Hospital, QLD, Australia and Prince Charles Hospital, QLD, Australia between 2005 and 2014. DNA from an additional 229 healthy control donors recruited from Western Australia (Temple et al., 2003)(Temple et al., 2003)(Temple et al., 2003) (Temple et al., 2003) was provided by the Institute for Respiratory Health, Western Australia.

A strong association between pulmonary NTM disease and a polymorphism within IL10 (rs1518111), and a haplotype spanning the three genes P2X4R, P2X7R and CAMKK2 were identified. These results implicate these genes (or other genes in linkage disequilibrium with them) and their products as factors contributing to infection and disease. This information may prove critical in developing new strategies and therapies for patients with NTM disease and may provide critical insights into other mycobacterial diseases such as leprosy and tuberculosis.
Keyword Nontuberculous mycobacteria (NTM)
Pulmonary disease
Genetic polymorphism
Epidemiology
Environment
IL10

Document type: Thesis
Collections: UQ Theses (RHD) - Official
UQ Theses (RHD) - Open Access
 
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Created: Sat, 20 May 2017, 18:00:19 EST by Samuel Halstrom on behalf of Learning and Research Services (UQ Library)