Article
Polymorphisms in IL-1beta, vitamin D receptor Fok1, and Toll-like receptor 2 are associated with extrapulmonary tuberculosis
Registro en:
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.
1471-2350
10.1186/1471-2350-11-37
Autor
Motsinger-Reif, Alison A.
Antas, Paulo R. Z.
Oki, Noffisat O.
Levy, Shawn
Holland, Steven M.
Sterling, Timothy R.
Resumen
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.
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