Association between vitamin D receptor gene polymorphisms and response to treatment of pulmonary tuberculosis.
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.
Roth
Daniel E
DE
Asociación Benéfica Proyectos en Informática, Salud, Medicina y Agricultura, Cayetano Heredia University, Lima, Peru.
Soto
Giselle
G
Arenas
Fanny
F
Bautista
Christian T
CT
Ortiz
Jaime
J
Rodriguez
Richard
R
Cabrera
Lilia
L
Gilman
Robert H
RH
D000293:Adolescent; D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D015252:Deoxyribonucleases, Type II Site-Specific; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D010568:Peru; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D018167:Receptors, Calcitriol / Q000235:genetics*; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*
D000995:Antitubercular Agents; D018167:Receptors, Calcitriol; C035042:endodeoxyribonuclease FokI; D015252:Deoxyribonucleases, Type II Site-Specific; C027046:TCGA-specific type II deoxyribonucleases