[On the association of tumor necrosis factor-alpha gene polymorphisms with the susceptibility to silicosis].
ABSTRACT To find out whether -308 and -238 locus (G --> A) mutation within the tumor necrosis factor-alpha gene (TNF-alpha) promoter region are associated with susceptibility to silicosis in the Han population of southwest China.
Governed by the principles of voluntatiness and cooperation, 75 patients with silicosis and 137 control with silica-exposure but without silicosis were recruited, and additionally, 140 elderly patients with silicosis and 135 healthy elderly (retired) controls were recruited in this case-control study. 5 ml peripheral vein blood was drawn from each subject. By means of polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) and sequencing techniques, TNF-alpha gene polymorphisms of all subjects were analyzed.
The frequencies of TNF-alpha -308A and -238A in the 75 patients with silicosis were higher than those in the 137 controls (P < 0.01). After being adjusted for confounding factors, the -308A and the -238A were still associated with the presence of silicosis (P < 0.01). But the frequency of TNF-alpha -308A in the 140 elderly patients was significantly lower than that in the controls (P < 0.001).
TNF-alpha gene -308 and -238 locus (G --> A) mutation might be related to the occurrence of silicosis and the severity of pulmonary fibrosis in silicosis among the Han population of southwest China, and TNF2 (-308A) allele might increase the risk of the disease.
- SourceAvailable from: Harapan Harapan, MD
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- "including eleven SNPs in promoter region À1031 (T/C), À863 (C/A), À857 (C/T), À308 (G/A), À238 (G/A), À1196 (C/T), À1125 (G/C), À572 (A/C), À316 (G/A), À163 (G/A), and À70 (G/A)   "
ABSTRACT: Several epidemiology studies suggest that host genetic factors play important roles in susceptibility, protection and progression of tuberculosis infection. Here we have reviewed the implications of some genetic polymorphisms in pathways related to tuberculosis susceptibility, severity and development. Large case-control studies examining single-nucleotide polymorphisms (SNPs) in genes have been performed in tuberculosis patients in some countries. Polymorphisms in natural resistance-associated macrophage protein 1 (NRAMP1), toll-like receptor 2 (TLR2), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-a), interleukin-1 receptor antagonist (IL-1RA), IL-10, vitamin D receptor (VDR), dendritic cell-specific ICAM-3-grabbing non-integrin (DC-SIGN), monocyte chemoattractant protein-1 (MCP-1), nucleotide oligomerization binding domain 2 (NOD2), interferon-gamma (IFN-c), inducible nitric oxide synthase (iNOS), mannosebinding lectin (MBL) and surfactant proteins A (SP-A) have been reviewed. These genes have been variably associated with tuberculosis infection and there is strong evidence indicating that host genetic factors play critical roles in tuberculosis susceptibility, severity and development.12/2013; 63(1). DOI:10.1016/j.ejcdt.2013.12.002
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- "Cytokine polymorphisms of TNF-α were found to be associated with the silicosis risk in the Chinese workers exposed to silica particles . Other several studies also have different conclusions [31-35]. "
ABSTRACT: Tumor necrosis factor-α (TNF-α) 308 G/A gene polymorphism has been reported to be associated with susceptibility to silicosis. However, the relevant study results are still inconsistent. A meta-analysis was performed in order to drive a more precise estimation of the relationship between TNF-α-308 G/A gene polymorphism and susceptibility to silicosis. Electronic databases were searched and nine separate studies were included. The pooled odds ratios (ORs) and the corresponding 95% confidence internal (CI) were calculated by a fixed effect model. A total of 1267 cases and 1214 controls were included. In the overall analysis, significantly increased silicosis risk was found (for GA+AA vs. GG OR=1.45, 95%CI: 1.20-1.760, P=1.58E4; for GA vs. GG: OR=1.53, 95%CI=1.25-1.86, P=3.11E5; for A allele vs. G allele: OR=1.27, 95%CI=1.08-1.50, P= 0.004). In the subgroup analysis, significantly increased silicosis risk was also found among Asians (for GA+AA vs. GG: OR=1.63, 95%CI=1.27-2.08, P=1.01E4), for GA vs. GG: OR=1.71, 95%CI=1.33-2.20, P=3.44E5), for A allele vs. G allele: OR=1.45, 95%CI=1.17-1.80, P=0.001). However, no significantly increased risk was found among non-Asians for all genetic models. TNF-α-308 G/A polymorphism might lead to an increased risk of silicosis susceptibility, especially for Asians. However, further studies with large sample sizes should be conducted to confirm the association.PLoS ONE 10/2013; 8(10):e76614. DOI:10.1371/journal.pone.0076614 · 3.23 Impact Factor
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ABSTRACT: Tumour necrosis factor (TNF)-alpha influences the pathogenesis of lung fibrosis and carcinogenesis in normal cells. Polymorphisms of this gene have been suggested to be associated with susceptibility to lung diseases. Association studies were performed in German subjects, using control subjects (n = 177), pulmonary fibrosis patients (n = 612) and bronchial carcinoma patients (n = 374). Compared with a healthy (control) group, a significant result could be obtained for the asbestosis (patient) group (crude odds ratio (OR(crude)) = 1.57; 95% confidence interval (CI) 1.05-2.36; p = 0.03), especially with severe lung asbestosis (OR(crude) = 4.15; 95% CI 1.06-16.16; p = 0.04). A significant association was revealed when comparing asbestosis patients (OR(crude) = 4.08; 95% CI 1.53-10.54; p = 0.004 and OR(adjusted) = 3.89; 95% CI 1.49-10.17; p = 0.006) with asbestos-induced lung cancer patients. The results confirm the hypothesis that TNF-alpha polymorphisms are associated with asbestos-induced fibrotic or malignant lung diseases in Germans.Biomarkers 08/2010; 15(5):400-9. DOI:10.3109/1354750X.2010.481365 · 2.52 Impact Factor