Pharmacogenetics of Vitamin D Supplementation in Tuberculosis

The 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:

1. Patients being managed with regimes outside standard NICE guidance
2. Drug resistant MTb
3. HIV positive
4. Known intolerance of vitamin D
5. Sarcoidosis
6. Hyperparathyroidism or nephrolithiasis
7. Taking vitamin D supplementation in the two months preceding enrolment
8. Baseline serum corrected calcium >2.65 mmol/L
9. Current haemodialysis
10. Children, pregnant or breastfeeding individuals
11. Concomitant benzothiadiazine derivative, cardiac glycoside, carbamazepine, phenobarbital, phenytoin, primidone or long-term immunosuppressant therapy