We investigated the role of DC-SIGN (CD209), long pentraxin 3 (PTX3) and vitamin D receptor (VDR) gene single nucleotide polymorphisms (SNPs) in susceptibility to pulmonary tuberculosis (TB) in 321 TB cases and 347 healthy controls from GuineaBissau. Five additional, functionally relevant SNPs within toll-like receptors (TLRs) 2, 4 and 9 were typed but found, when polymorphic, not to affect host vulnerability to pulmonary TB. We did not replicate an association between SNPs in the DC-SIGN promoter and TB. However, we found that two polymorphisms, one in DC-SIGN and one in VDR, were associated in a nonadditive model with disease risk when analyzed in combination with ethnicity (P ¼ 0.03 for DC-SIGN and P ¼ 0.003 for VDR). In addition, PTX3 haplotype frequencies significantly differed in cases compared to controls and a protective effect was found in association with a specific haplotype (OR 0.78, 95% CI 0.63-0.98). Our findings support previous data showing that VDR SNPs modulate the risk for TB in West Africans and suggest that variation within DC-SIGN and PTX3 also affect the disease outcome.
Vitamin D does not improve clinical outcome among patients with TB and the trial showed no overall effect on mortality in patients with TB; it is possible that the dose used was insufficient. Clinical trial registered with www.controlled-trials.com/isrctn (ISRCTN35212132).
Hypovitaminosis D was highly prevalent in TB patients and in healthy controls living at 12 degrees N; severe VDD was rare in TB patients. The finding indicates that the serum 25(OH)D(3) concentration is associated with TB infection, but whether this role is a symptom or is causal was not established.
Background: IFN-γ responses to M. tuberculosis antigens are used as in-vitro diagnostic tests for tuberculosis infection. The tests are highly specific but sensitivity may be impaired due to immunosuppression. The objective of this small exploratory study was to compare three novel biomarkers for in-vitro diagnosis of tuberculosis -MCP-1, MCP-3 and IL-1RA -with the current established biomarker IFN-γ and the newly described IP-10 and MCP-2.
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