MDR TB vit D receptor

MDR TB vit D receptor

Risk and outcome of multidrug-resistant tuberculosis: vitamin D receptor polymorphisms and serum 25(OH)D

Tuberculosis (TB) is a global public health problem. In 2010, approximately 8.8 million new cases were diagnosed worldwide (around 2 million in India). Multidrug-resistant TB (MDR-TB, in which resistance to at least the two most potent first-line drugs (rifampicin and isoniazid) is observed, is an escalating problem, with around 650 000 cases prevalent worldwide in 2010.

1,25-hydroxyvitamin D, which primarily regulates calcium physiology, also acts as an immunoregulator. In recent years, it has been linked to a wide range of diseases with regard to 25(OH)D serum levels, genetic susceptibility and therapeutics. Therefore, researchers from All India Institute of Medical Sciences and Rajan Babu Institute of Pulmonary Medicine and Tuberculosis, New Delhi, India conducted a cross-sectional study in July 2006-January 2011.

The aim of that study is to investigate the association of vitamin D receptor (VDR) polymorphisms and serum 25(OH)D with susceptibility to, and response to treatment of, multidrug-resistant tuberculosis (MDR-TB) in comparison with drug-susceptible pulmonary TB (DS-PTB) and healthy controls.

This study involved 897 sputum positive pulmonary TB patients. They were divided into 3 groups: MDR-TB 354, drug-susceptible pulmonary TB (DS-PTB) 338, controls 205. Patients with sputum smear and culture-positive pulmonary TB, with drug susceptibility testing (DST) revealing MDR strains of TB, were enrolled into the MDR-TB group. The drug susceptible group comprised newly diagnosed sputum smear- and culture-positive pulmonary cases, with baseline susceptibility to all first-line anti-tuberculosis drugs.

Genotypic and allelic frequencies of FokI, BsmI and TaqI VDR poly morphisms, and serum 25(OH)D, calcium and intact parathyroid hormone were measured in all participants. In those with active TB, disease severity, time to sputum smear and culture conversion were correlated with VDR genotype and biochemical parameters.

The result from this study demonstrated that FokI Ff genotype and TaqI t allele correlated positively with MDR-TB (OR:1.86 and 1.99); ff genotype and f allele of FokI frequency were higher in both TB groups. BsmI Bb genotype correlated inversely with MDR-TB. In addition, serum 25(OH)D concentrations were significantly lowest in MDR-TB, correlating inversely with time to sputum smear conversion.

Based on the result of this study, researchers concluded that there were a significant association of VDR polymorphisms and low serum 25(OH)D with presence of MDR-TB as compared to DS-PTB and healthy controls. This suggests that VDR polymorphisms and low serum 25(OH)D levels may be linked to susceptibility to MDR-TB, at least in Indians. The TaqI t allele’s apparent association with multidrug resistance means that it may play a role as a risk factor for the development of MDR-TB.

Rathored J, Sharma SK, Singh B, Banavaliker JN, Sreenivas V, Srivastava AK, et al. Risk and outcome of multidrug-resistant tuberculosis: vitamin D receptor polymorphisms and serum 25(OH)D. Int J Tuberc Lung Dis. 2012;16(11):1522–28.