Toll-like receptors, tumor necrosis factor-α, and interleukin-10 gene polymorphisms in risk of pulmonary tuberculosis and disease severity.

Toll-like receptors (TLRs) and cytokines play key roles in innate and adaptive immunity against Mycobacterium tuberculosis (M.TB). The aim of this study was to investigate whether the functional genetic variations at position 1805 G/T in TLR1, 2258 A/G in TLR2, -857 C/T, and -863 A/C in tumor necrosis factor-α (TNF-α), as well as -819 C/T in interleukin-10 (IL-10) confer susceptibility to pulmonary tuberculosis (PTB). We performed a hospital-based case-control study using 543 case patients and 544 controls. Multivariate logistic regression analysis revealed that the TT genotype of -857 C/T in TNF-α gene was significantly associated with lower risk of PTB, in comparison with other genotypes (odds ratios [OR] = 0.68, 95% confidence interval [CI] = 0.53-0.86, p = 0.001). Conversely, the genetic variants of -863 A/C in TNF-α gene was associated with susceptibility to PTB (OR = 2.42%, 95% CI = 1.28-4.59, p = 0.007) and clinical severity of disease (OR = 3.59%, 95% CI = 1.41-9.11, p = 0.007). Our results indicated that the variants in TNF-α gene were associated with susceptibility to PTB and clinical severity of disease, whereas no significance could be inferred from TLRs and IL-10 genes polymorphisms. Crown Copyright 2010. Published by Elsevier Inc. All rights reserved.