Association between Vitamin D Receptor Gene Polymorphisms and Response to Treatment of Pulmonary Tuberculosis

• Published in: The Journal of infectious diseases Vol. 190; no. 5; pp. 920 - 927
• Main Authors: Roth, Daniel E., Soto, Giselle, Arenas, Fanny, Bautista, Christian T., Ortiz, Jaime, Rodriguez, Richard, Cabrera, Lilia, Gilman, Robert H.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01.09.2004; University of Chicago Press; Oxford University Press
• Subjects: Adolescent; Adult; Alleles; Antitubercular Agents - therapeutic use; Bacteria; Biological and medical sciences; Case control studies; Cohort studies; Deoxyribonucleases, Type II Site-Specific; Fundamental and applied biological sciences. Psychology; Genetic Predisposition to Disease; Genotypes; Humans; Incidence; Infectious diseases; Medical sciences; Microbiology; Middle Aged; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; Peru; Polymorphism, Genetic; Prospective Studies; Pulmonary tuberculosis; Receptors; Receptors, Calcitriol - genetics; Sputum; Treatment Outcome; Tuberculosis; Tuberculosis, Pulmonary - drug therapy; Tuberculosis, Pulmonary - epidemiology; Tuberculosis, Pulmonary - genetics; Vitamin D; Peru; Infection; Lung disease; Treatment; Gene; Microbiology; Vitamin D; Respiratory disease; Pulmonary tuberculosis; Bacteriosis; Mycobacterial infection; Polymorphism
• DOI: 10.1086/423212
• ISSN: 0022-1899

Background. Polymorphisms in the gene that encodes the vitamin D receptor (VDR) may influence the host response to Mycobacterium tuberculosis infection. Methods. In a Peruvian community with a high incidence of tuberculosis (TB), VDR TaqI and FokI polymorphisms were compared among 103 patients with pulmonary TB and 206 matched healthy control subjects. Associations of VDR polymorphisms with treatment outcome were analyzed among 78 patients undergoing treatment of pulmonary TB. Results. Sputum mycobacterial culture and auramine stain conversions were significantly faster among participants with the FokI FF genotype, compared with participants with the non-FF genotypes. Sputum culture conversion was faster among participants with the TaqI Tt genotype, compared with those with the TT genotype. Increased probability of culture conversion during TB treatment was independently associated with the TaqI Tt genotype (age- and sex-adjusted relative risk, 4.28; 95% confidence interval, 1.88–9.75; P = .001). VDR polymorphisms were not significantly associated with susceptibility to TB in the case-control study. Conclusions. VDR gene polymorphisms are associated with the time to sputum culture and auramine stain conversion during TB treatment. To our knowledge, the present study is the first report of a specific host gene influence on the outcome of TB treatment. These findings demonstrate the potential clinical relevance of immunomodulatory functions of vitamin D metabolites acting via the VDR in the host response against pulmonary TB.