Vitamin D receptor gene polymorphisms and sputum conversion time in pulmonary tuberculosis patients

Abstract

A cohort of pulmonary tuberculosis (TB) patients in a South African admixed population was investigated to determine if the vitamin D receptor gene (VDR) polymorphisms FokI, ApaI, and TaqI are associated with TB susceptibility or time to sputum conversion, and to investigate other clinical and demographic factors affecting the rate of response to treatment. Firstly, a case-control association study of 249 TB cases and 352 healthy controls was carried out to investigate association of VDR polymorphisms with TB susceptibility. Secondly, a cohort of pulmonary tuberculosis patients with conversion times for both sputum smear (n=220) and culture (n=222) were analysed to determine factors contributing to mycobacterial resolution in sputum. Age and gender adjusted Cox regression models were constructed. Our results indicate that the extent of disease at diagnosis was predictive of both smear and culture conversion times in the final models. Smoking status and VDR genotype contributed independently to smear conversion time, with ApaI 'AA' genotype and TaqI 'T'-containing genotypes predictive of a faster response to TB chemotherapy. We did not find an association between VDR genotype and TB in the case-control study. We conclude that the time taken for an individual to convert to sputum negativity while on antituberculosis therapy can be independently predicted by the VDR genotype.