Pharmacogenetics of Vitamin D Supplementation in Tuberculosis

Previous studies of vitamin D supplementation have suggested there may be differences in response between individuals. This study is an open label study of vitamin D supplementation in patients with active or latent tuberculosis in which active disease patients take 100000units of vitamin D every 8 weeks during their tuberculosis treatment. Genotyping for relevant vitamin D pathway polymorphisms will be carried out and related to clinical and ex vivo markers of vitamin D response. Latent patients will only be studied for vitamin D response ex vivo. Our hypothesis is that response to vitamin D in both monocytes and T cells will be related to polymorphisms in the DBP gene, and that this may relate to clinical response in terms of post supplementation vitamin D level.

Inclusion Criteria: Age 16 or above Microbiologically or histologically confirmed active tuberculosis Clinically confirmed latent tuberculosis Exclusion Criteria: Patients being managed with regimes outside standard NICE guidance Drug resistant MTb HIV positive Known intolerance of vitamin D Sarcoidosis Hyperparathyroidism or nephrolithiasis Taking vitamin D supplementation in the two months preceding enrolment Baseline serum corrected calcium >2.65 mmol/L Current haemodialysis Children, pregnant or breastfeeding individuals Concomitant benzothiadiazine derivative, cardiac glycoside, carbamazepine, phenobarbital, phenytoin, primidone or long-term immunosuppressant therapy