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.
Ma
Mai-juan
MJ
Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing, China.
Xie
Lan-pin
LP
Wu
Shu-cai
SC
Tang
Fang
F
Li
Hao
H
Zhang
Zheng-shan
ZS
Yang
Hong
H
Chen
Su-li
SL
Liu
Ning
N
Liu
Wei
W
Cao
Wu-chun
WC
D000328:Adult; D002681:China; D018450:Disease Progression; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D011110:Polymorphism, Genetic; D012306:Risk; D051193:Toll-Like Receptors / Q000235:genetics*; D014397:Tuberculosis, Pulmonary / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10