| Author | Motsinger-Reif, Alison A. | |
| Author | Antas, Paulo R. Z. | |
| Author | Oki, Noffisat O. | |
| Author | Levy, Shawn | |
| Author | Holland, Steven M. | |
| Author | Sterling, Timothy R. | |
| Access date | 2018-05-17T13:52:37Z | |
| Available date | 2018-05-17T13:52:37Z | |
| Document date | 2010 | |
| Citation | MOTSINGER-REIF, Alison A. et al. Polymorphisms in IL-1b, vitamin D receptor Fok1, and Toll-like receptor 2 are associated with extrapulmonary tuberculosis. BMC Medical Genetics, v.11:37, 10p, 2010. | pt_BR |
| ISSN | 1471-2350 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/26470 | |
| Language | eng | pt_BR |
| Publisher | BioMed Central | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Tuberculose | pt_BR |
| Subject in Portuguese | Tuberculose extrapulmonar | pt_BR |
| Subject in Portuguese | Polimorfismos | pt_BR |
| Subject in Portuguese | Receptor 2 Toll-Like | pt_BR |
| Subject in Portuguese | Genética Humana | pt_BR |
| Title | Polymorphisms in IL-1beta, vitamin D receptor Fok1, and Toll-like receptor 2 are associated with extrapulmonary tuberculosis | pt_BR |
| Type | Article | |
| DOI | 10.1186/1471-2350-11-37 | |
| Abstract | Background: Human genetic variants may affect tuberculosis susceptibility, but the immunologic correlates of the
genetic variants identified are often unclear.
Methods: We conducted a pilot case-control study to identify genetic variants associated with extrapulmonary
tuberculosis in patients with previously characterized immune defects: low CD4+ lymphocytes and low
unstimulated cytokine production. Two genetic association approaches were used: 1) variants previously associated
with tuberculosis risk; 2) single nucleotide polymorphisms (SNPs) in candidate genes involved in tuberculosis
pathogenesis. Single locus association tests and multifactor dimensionality reduction (MDR) assessed main effects
and multi-locus interactions.
Results: There were 24 extrapulmonary tuberculosis cases (18 black), 24 pulmonary tuberculosis controls (19 black)
and 57 PPD+ controls (49 black). In approach 1, 22 SNPs and 3 microsatellites were assessed. In single locus
association tests, interleukin (IL)-1b +3953 C/T was associated with extrapulmonary tuberculosis compared to PPD+
controls (P = 0.049). Among the sub-set of patients who were black, genotype frequencies of the vitamin D
receptor (VDR) Fok1 A/G SNP were significantly different in extrapulmonary vs. pulmonary TB patients (P = 0.018).
In MDR analysis, the toll-like receptor (TLR) 2 microsatellite had 76% prediction accuracy for extrapulmonary
tuberculosis in blacks (P = 0.002). In approach 2, 613 SNPs in 26 genes were assessed. None were associated with
extrapulmonary tuberculosis.
Conclusions: In this pilot study among extrapulmonary tuberculosis patients with well-characterized immune
defects, genetic variants in IL-1b, VDR Fok1, and TLR2 were associated with an increased risk of extrapulmonary
disease. Additional studies of the underlying mechanism of these genetic variants are warranted. | pt_BR |
| Affilliation | North Carolina State University. Bioinformatics Research Center. Department of Statistics. Raleigh, NC, USA. | pt_BR |
| Affilliation | Vanderbilt University School of Medicine. Department of Medicine. Division of Infectious Dieseases. Nashville, Tennessee, USA | pt_BR |
| Affilliation | North Carolina State University. Bioinformatics Research Center. Department of Statistics. Raleigh, NC, USA. | pt_BR |
| Affilliation | Vanderbilt University School of Medicine. Department of Biomedical Informatics. Nashville, Tennessee, USA. | pt_BR |
| Affilliation | National Institutes of Health. Laboratory of Clinical Infectious Diseases. Bethesda, MD, USA. | pt_BR |
| Affilliation | Vanderbilt University School of Medicine. Department of Medicine. Division of Infectious Dieseases. Nashville, Tennessee, USA / Vanderbilt University School of Medicine. Department of Medicine.. Center for Health Services Research. Nashville, TN, USA.. Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Clínica. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | extrapulmonary tuberculosis | pt_BR |
| Subject | Polymorphisms | pt_BR |
| Subject | human genetics | pt_BR |
| Subject | vitamin D receptor Fok1 | pt_BR |
| Subject | Toll-like receptor 2 | pt_BR |
