Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.725457
Title: The pharmacogenetic and immunomodulatory response to Vitamin D in tuberculosis
Author: Hawthorne, Gemma Mary
ISNI:       0000 0004 6423 7429
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2017
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Abstract:
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. Aims 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. Results 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. Conclusion 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.
Supervisor: Not available Sponsor: University Hospital Birmingham Charities
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.725457  DOI: Not available
Keywords: QH426 Genetics ; QR180 Immunology ; RC Internal medicine
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