The pharmacogenetic and immunomodulatory response to Vitamin D in tuberculosis

Hawthorne, Gemma Mary (2017). The pharmacogenetic and immunomodulatory response to Vitamin D in tuberculosis. University of Birmingham. M.D.

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Tuberculosis is a global problem, with little change in antibiotic therapy over the last fifty years, but with the emergence of both multi-drug resistant disease and extensive drug resistant disease further treatments are needed to ensure successful management of the disease.
Severe vitamin D deficiency is prevalent in patients with tuberculosis and the immunomodulatory mechanisms of elements of the vitamin D axis, including vitamin D binding protein (DBP) and vitamin D receptor (VDR) have been explored in part.
This thesis will ascertain the role of polymorphisms in vitamin D axis genes in determining response to vitamin D in tuberculosis patients. Additionally it will aim to determine whether the interaction between underlying genotype, baseline vitamin D level and other elements of the vitamin D axis has the potential to influence clinical outcome and further investigate in vitro effects of vitamin D and elements of the vitamin D axis in influencing the frequency and functionality of monocytes and T cells, both of which are key elements in the immune response to tuberculosis infection.
Associations between vitamin D baseline and response to supplementation appear to have a genetic association with DBP, VDR and DHCR7 genotypes and varying DBP haplotypes appear to determine the level of DBP at baseline measurement. The effect of vitamin D has an immunomodulatory role in both monocyte response and T regulatory activity, with a clear effect of vitamin D on cytokine response.
There appears to be a role for vitamin D in the treatment of tuberculosis but further questions are raised regarding the benefits and risks of immune response modulation in an inflammatory/ cytopathogenic condition such as tuberculosis.

Type of Work: Thesis (Higher Doctorates > M.D.)
Award Type: Higher Doctorates > M.D.
College/Faculty: Colleges (2008 onwards) > College of Medical & Dental Sciences
School or Department: School of Clinical and Experimental Medicine
Funders: Other
Other Funders: University Hospitals Birmingham Charity
Subjects: Q Science > QH Natural history > QH426 Genetics
Q Science > QR Microbiology > QR180 Immunology
R Medicine > RC Internal medicine


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