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

Abstract

SETTING: All India Institute of Medical Sciences and Rajan Babu Institute of Pulmonary Medicine and Tuberculosis, New Delhi, India. OBJECTIVE: 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. DESIGN: Cross-sectional study. METHODS: A total of 897 participants from northern India were consecutively enrolled into three groups (MDR-TB 354, DS-PTB 338, controls 205). Genotypic and allelic frequencies of FokI, BsmI and TaqI VDR polymorphisms, 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. RESULTS: FokI Ff genotype and TaqI t allele correlated positively with MDR-TB; Ff genotype and f allele of FokI frequency were higher in both TB groups. BsmI Bb genotype correlated inversely with MDR-TB. Serum 25(OH)D concentrations were significantly lowest in MDR-TB, correlating inversely with time to sputum smear conversion. CONCLUSIONS: VDR gene polymorphisms and hypovitaminosis D may predispose to MDR-TB. Lower serum 25(OH)D may increase time to MDR-TB sputum smear negativity.