Association of vitamin D receptor mRNA expression, vitamin D deficiency and genetic variant in patients with multi-drug resistant pulmonary tuberculosis.

BACKGROUND: Multi-drug resistant pulmonary tuberculosis (MDR-TB), is a serious threat to world health. Serum levels of vitamin D, a ligand for the VDR that controls VDR mRNA expression, are still poorly understood in MDR-TB.

OBJECTIVE: To study the association of mRNA expression with low vitamin D levels and VDR polymorphisms in patients with MDR-TB compared to normal controls.

METHODS: Study groups consisted of sputum smears and culture-positive MDR-TB at two hospitals in New Delhi, and normal controls were enrolled from a North Indian population. A total 100 (50 MDR-TB subjects and 50 controls) were consecutively enrolled. VDR mRNA expression in peripheral blood mononuclear cells (PBMC) was analysed by Real-time PCR. Serum 25-hydroxyvitamin D, intact parathyroid hormone (iPTH), and calcium (ionized and total) levels were measured, and the correlation between variables was determined. The association between VDR genotype and VDR mRNA expression was studied between MDR-TB and normal controls together with the genotypic and allelic frequencies of the FokI, BsmI, and TaqI VDR polymorphisms were also assessed in between the two groups.

RESULTS: To investigate the role of VDR gene expression and FokI polymorphism in MDR-TB, a total of 100 patients were split into two groups. VDR mRNA expression significantly decreased in MDR-TB patients, being 0.6 times lower than in healthy controls. Notably, the ff genotype was associated with reduced VDR expression, indicating a functional impact on gene regulation. However, there was no appreciable variation in the groups' distribution of FokI alleles and genotypes. These findings highlight the importance of merging genetic and expression data, showing that while the ff variation influences individual expression, it does not distinguish MDR-TB patients from controls.

CONCLUSION: In present study, the VDR gene's FokI polymorphism affects the levels of VDR mRNA expression, with the ff genotype linked to lower expression in both MDR-TB patients and healthy individuals. Nonetheless, there were no appreciable differences in the genotypic and allelic frequencies of FokI between the groups. These findings suggest that the location of the FokI variation in the population may not be as important to MDR-TB susceptibility as its functional impact on gene expression.