Association of Fok1 VDR polymorphism with Vitamin D and its associated molecules in pulmonary tuberculosis patients and their household contacts

Abstract

Status of Fok I VDR polymorphism along with vitamin D, Vitamin D receptor (VDR), and cathelicidin levels in Tuberculosis (TB) patients compared to household contacts and implication of these findings in susceptibility to TB is not known. 150 active TB patients, 150 household contacts and 150 healthy controls were recruited from North Indian population. Fok1 VDR polymorphism was studied by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP).VDR mRNA and protein levels were studied using quantitative real time PCR (q rt PCR) and enzyme linked immunosorbent assay (ELISA) respectively. Cathelicidin and Vitamin D levels were measured using ELISA and chemiluminescence immunoassay (CLIA) respectively. Significant association was found between Fok1 polymorphism and susceptibility to TB (P < 0.0005). VDR mRNA, VDR protein and vitamin D levels were significantly lower in active TB group when compared to household contacts and healthy controls (P < 0.0001, 0.0001 and 0.0005 respectively). Cathelicidin levels were higher in active TB patients compared to other groups (P < 0.0001). Expression of VDR and cathelicidin was significantly higher among ‘FF’ genotypes of VDR (more active form of VDR) compared to ‘ff’ genotype (less active form of VDR). ‘f’ allele was associated with increased susceptibility to TB. Higher frequency of ‘F’ allele, increased VDR expression along with increased vitamin D levels in household contacts compared to active TB group might be responsible for protection against active TB.

Impact of vitamin D status and cathelicidin antimicrobial peptide on adults with active pulmonary TB globally: A systematic review and meta-analysis

“…Accordingly, results of vitamin D deficiency estimated by 25(OH) D levels from nine studies reported low levels among the TB patients. Six studies reported vitamin D deficiency levels of > 20 ng/ml [ 5 , 11 , 15 , 29 , 33 , 39 ] and three reported insufficient levels between 21–29 ng/ml [ 38 , 41 , 42 ]. Conversely, severe vitamin D deficiency as low as >10 ng/ml was reported by a study from Russia [ 43 ].…”

“…Eight studies measured circulatory LL-37 levels in both serum and plasma samples. Of these, six studies reported higher circulatory LL-37 levels in TB patients compared to the non-TB individuals [ 5 , 11 , 29 , 33 , 39 , 41 ]. Two studies found lower serum LL-37 levels in TB patients compared to non -TB individuals [ 38 , 42 ].…”

“…Worldwide research suggests that vitamin D deficiency (VDD) is found at all ages and has been linked to infectious and non-infectious diseases [ 5 – 8 ]. Moreover, vitamin D3 may be obtained from sunshine exposure and vitamin D2 form is acquired from the diet and eventually synthesized and converted to immunomodulatory 1, 25 Dihydroxy vitamin D3 (1, 25(OH) D3) [ 6 , 9 – 11 ]. Nonetheless, the widely accepted indicator for vitamin D status is 25(OH) D [ 12 – 14 ].The involvement of vitamin D in protection against TB is demonstrated by the modulation of both innate and adaptive immune responses [ 15 – 17 ].…”

Immunomodulatory Role of Vitamin D: Clinical Implications in Infections and Autoimmune Disorders

“…8,15 Tuberculosis has been linked with vitamin D deficiency and VDR polymorphisms which make these populations particularly susceptible to the ailment. [16][17][18] Progression of TB in affected individuals has a strong correlation with serum vitamin D levels. 19 This may be explained by the bactericidal action of vitamin D against Mycobacterium tuberculosis such as reversal of mycobacterium tuberculosis-induced inhibition of phagosome maturation, which is an important element of progression of tu-berculosis.…”

Vitamin D3 receptor polymorphisms regulate T cells and T cell-dependent inflammatory diseases

“…These naturally occurring polymorphisms are exclusively active in immune cells, offering a unique platform to study the immunomodulatory properties of VDR in a physiological context, without systemic vitamin D-related effects. Overexpression of VDR enhances T cell-driven inflammation in mice and associates with autoimmune arthritis in humans (8)(9)(10). These observations suggest that even highly localized VDR expression levels in inflammatory conditions, rather than 25(OH)D 3 availability, could be associated with a poor disease prognosis in autoimmune patients.…”