Influence of vitamin D deficiency and vitamin D receptor polymorphisms on tuberculosis among Gujarati Asians in west London: a case-control study

Background Susceptibility to disease after infection by Mycobacterium tuber culosis is influenced by environmental and host genetic factors. Vitamin D metabolism leads to activation of macrophages and restricts the intracellul ar growth of M tuberculosis. This effect may be influenced by polymorphisms at three sites in the Vitamin D receptor (VDR) gene. We investigated the i nteraction between serum vitamin D (25-hydroxycholecalciferol) concentratio ns and VDR genotype on susceptibility to tuberculosis. Methods This study was a hospital-based case-control analysis of Asians of Gujarati origin, a mainly vegetarian immigrant population with a high rate of tuberculosis. We typed three VDR polymorphisms (defined by the presence of restriction endonuclease sites for Taq1, Bsm1, and Fok1) in 91 of 126 un treated patients with tuberculosis and 116 healthy contacts who had been se nsitised to tuberculosis. Serum 25-hydroxycholecalciferol was recorded in 4 2 contacts and 103 patients. Findings 25-hydroxycholecalciferol deficiency was associated with active tu berculosis (odds ratio 2.9 [95% CI 1.3-6.5], p=0.008), and undetectable ser um 25-hydroxycholecalciferol (<7 nmol/L) carried a higher risk of tuberculo sis (9.9 [1.3-76.2], p=0.009). Although there was no significant independen t association between VDR genotype and tuberculosis, the combination of gen otype TT/Tt and 25-hydroxycholecalciferol deficiency was associated with di sease (2.8 [1.2-6.5]) and the presence of genotype ff or undetectable serum 25-hydroxycholecalciferol was strongly associated with disease (5.1[1.4-18 .4]). Interpretation 25-hydroxycholecalciferol deficiency may contribute to the h igh occurrence of tuberculosis in this population. Polymorphisms in the VDR gene also contribute to susceptibility when considered in combination with 25 hydroxycholecalciferol deficiency.