The pharmacogenetic and immunomodulatory response to Vitamin D in tuberculosis

[摘要] 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.

[发布机构] University:University of Birmingham;Department:School of Clinical and Experimental Medicine

[关键词] Q Science;QH Natural history;QH426 Genetics