Time-/dose- series transcriptome data analysis and traditional Chinese medicine treatment of pneumoconiosis.

Pneumoconiosis' pathogenesis is still unclear and specific drugs for its treatment are lacking. Analysis of series transcriptome data often uses a single comparison method, and there are few reports on using such data to predict the treatment of pneumoconiosis with traditional Chinese medicine (TCM). Here, we proposed a new method for analyzing series transcriptomic data, series difference analysis (SDA), and applied it to pneumoconiosis. By comparison with 5 gene sets including existing pneumoconiosis-related genes and gene set functional enrichment analysis, we demonstrated that the new method was not inferior to two existing traditional analysis methods. Furthermore, based on the TCM-drug target interaction network, we predicted the TCM corresponding to the common pneumoconiosis-related genes obtained by multiple methods, and combined them with the high-frequency TCM for its treatment obtained through literature mining to form a new TCM formula for it. After feeding it to pneumoconiosis modeling mice for two months, compared with the untreated group, the coat color, mental state and tissue sections of the mice in the treated group were markedly improved, indicating that the new TCM formula has a certain efficacy. Our study provides new insights into method development for series transcriptomic data analysis and treatment of pneumoconiosis.

Differential expression profile of microRNAs in the lung tissues of coal workers with pneumoconiosis and patients with silicosis.

The purpose of this study was to characterize the microRNA (miRNA) profile of the lung tissues from coal workers' pneumoconiosis (CWP) and silicosis and to analyze the changes in downstream genes, biological processes, and signaling pathways based on the differently expressed miRNAs. Lung tissues from three CWP patients, eight silicosis patients, and four healthy controls were collected and analyzed for their miRNA profiles using Affymetrix® GeneChip® miRNA Arrays. Differentially expressed miRNAs (DEMs) were identified between the different groups. The miRanda and TargetScan databases were used to predict the putative target genes, and volcano and heat maps were drawn. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were then performed to screen the DEMs-associated biological process and signaling pathways, respectively. Further identification with a comprehensive literature research involving particle exposure, fibrosis, inflammation and lung cancer were used to further screen DEMs of CWP and silicosis. Microarray data showed that 375 and 88 miRNAs were differentially expressed in CWP and silicosis lung tissues compared with healthy lung tissues, while 34 miRNAs were differentially expressed in CWP compared with silicosis lung tissues. The GO and KEGG pathway analyses showed that, the target genes were mainly enriched in the TGF-ß, MAPK, p53 and other signal pathways. These results provided insight into the miRNA-related underlying mechanisms of CWP and silicosis, and they provided new clues for miRNAs as biomarkers for the diagnosis and differential diagnosis of these two diseases.

Genetic susceptibility in pneumoconiosis in China: a systematic review.

OBJECTIVE: Pneumoconiosis, encompassing coal workers' pneumoconiosis (CWP), silicosis and asbestosis, is one of the most common occupational diseases in China. Previous studies revealed significant associations between genetic variations and pneumoconiosis risk among individuals in different countries. With the known variability of genetic makeup between ethnicities, susceptibility to pneumoconiosis due to genetic differences is likely to be ethnicity-specific. The present review aimed at providing a comprehensive overview on the association between genetic polymorphisms and susceptibility of pneumoconiosis, specifically among people in China. METHODS: The literature search was performed in seven English and Chinese databases using keywords related to the review aim. An appraisal of the methodological quality of the included studies was conducted using the assessment tool derived from the Strengthening the Reporting of Genetic Association Studies (STREGA) statement. RESULTS: Forty-five studies were included in this review. Genotypes of specific genes which are associated with the risk of CWP, silicosis and asbestosis were reported. Our findings showed that genes encoding inflammatory cytokines have been examined extensively, and they demonstrated an association between these genes and pneumoconiosis risk. Gene-environment interactions in pneumoconiosis susceptibility were also reported by a number of studies. CONCLUSIONS: This review summarised the evidence demonstrating the association between genetic polymorphisms and pneumoconiosis susceptibility among people in China, and that various genotypes could modify their risk to develop pneumoconiosis. The findings prompt that identification of individuals at high pneumoconiosis risk through genetic screening and strategies limiting their exposure to dust could be a potential strategy for the control of this occupational disease in China.

Epigenetic Changes and Functions in Pneumoconiosis.

Pneumoconiosis is one of the most common occupational diseases in the world, and specific treatment methods of pneumoconiosis are lacking at present, so it carries great social and economic burdens. Pneumoconiosis, coronavirus disease 2019, and idiopathic pulmonary fibrosis all have similar typical pathological changes-pulmonary fibrosis. Pulmonary fibrosis is a chronic lung disease characterized by excessive deposition of the extracellular matrix and remodeling of the lung tissue structure. Clarifying the pathogenesis of pneumoconiosis plays an important guiding role in its treatment. The occurrence and development of pneumoconiosis are accompanied by epigenetic factors (e.g., DNA methylation and noncoding RNA) changes, which in turn can promote or inhibit the process of pneumoconiosis. Here, we summarize epigenetic changes and functions in the several kinds of evidence classification (epidemiological investigation, in vivo, and in vitro experiments) and main types of cells (macrophages, fibroblasts, and alveolar epithelial cells) to provide some clues for finding specific therapeutic targets for pneumoconiosis and even for pulmonary fibrosis.

[Association between polymorphisms of interleukin-17 genes and pneumoconiosis susceptibility].

Objective: To explore the relationship between polymorphisms of interleukin 17(IL-17) gene (rs4711998, rs763780) and the susceptibility of pneumoconiosis, and to provide a basis for prevention of high-risk groups of pneumoconiosis. Methods: A total of 219 pneumoconiosis patients and 242 workers without pneumoconiosis were enrolled in the study. All subjects were photographed with high undulating X-rays anterior chest radiographs, diagnosed according to diagnostic criteria for pneumoconiosis. We collected 3 ml of peripheral venous blood of the study subjects. Polymorphism in IL-17A rs4711998 and IL-17F rs763780 locus were evaluated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The IL-17A rs4711998 locus has AA, AG and GG genotypes, there was no the significant difference between case and control groups (P>0.05). IL-17F rs763780 had AA, AG and GG genotypes, there was a significant difference between case and control groups (P<0.05). Allele A and allele G were statistically significant difference between the case group and the control group (P<0.05). Conclusion: No relationship was found between IL-17A gene polymorphisms at rs4711998 and silicosis. IL-17F rs763780 locus gene polymorphism is associated with susceptibility to pneumoconiosis. AG genotype and G allele may have a protective effect.

[Research of epigenetic modifications in pathogenesis of pneumoconiosis].

Pneumoconiosis is the most common and severe occupational disease, has become a major public health problem in the world. Its causes are well known, but the pathogenesis of it is not completely clear and effective therapies are not currently available. Epigenetic modifications have been considered an initial event in the development of pneumoconiosis. Epigenetic regulatory mechanisms in pneumoconiosis include DNA methylation, non-coding RNA (ncRNA) , and histone modification. In recent years, many researchers have studied the effect of dust-induced pulmonary fibrosis-related gene expression at the epigenetic level on macrophage activation, lung fibroblast proliferation, activation, transdifferentiation, and epithelial or endothelial-mesenchymal transition (EMT/EndMT) to further elucidate the pathogenesis of pneumoconiosis. In this review, we discusses the epigenetic modifications in pneumoconiosis, with an aim to provide new insights into the early diagnosis, condition assessment and targeted therapy of this occupational disease.

Functional variant of the carboxypeptidase M (CPM) gene may affect silica-related pneumoconiosis susceptibility by its expression: a multistage case-control study.

OBJECTIVES: In a genome-wide association study, we discovered chromosome 12q15 (defined as rs73329476) as a silica-related pneumoconiosis susceptibility region. However, the causal variants in this region have not yet been reported. METHODS: We systematically screened eight potentially functional single-neucleotide polymorphism (SNPs) in the genes near rs73329476 (carboxypeptidase M (CPM) and cleavage and polyadenylation specific factor 6 (CPSF6)) in a case-control study including 177 cases with silicosis and 204 healthy controls, matched to cases with years of silica dust exposure. We evaluated the associations between these eight SNPs and the development of silicosis. Luciferase reporter gene assays were performed to test the effects of selected SNP on the activity of CPM in the promoter. In addition, a two-stage case-control study was performed to investigate the expression differences of the two genes in peripheral blood leucocytes from a total of 64 cases with silicosis and 64 healthy controls with similar years of silica dust exposure as the cases. RESULTS: We found a strong association between the mutant rs12812500 G allele and the susceptibility of silicosis (OR=1.45, 95% CI 1.03 to 2.04, p=0.034), while luciferase reporter gene assays indicated that the mutant G allele of rs12812500 is strongly associated with increased luciferase levels compared with the wild-type C allele (p<0.01). Moreover, the mRNA (peripheral blood leucocytes) expression of the CPM gene was significantly higher in subjects with silicosis compared with healthy controls. CONCLUSIONS: The rs12812500 variant of the CPM gene may increase silicosis susceptibility by affecting the expression of CPM, which may contribute to silicosis susceptibility with biological plausibility.

Downregulation of exosomal let-7a-5p in dust exposed- workers contributes to lung cancer development.

BACKGROUND: Either chronic or acute exposure to dust particles may lead to pneumoconiosis and lung cancer, and lung cancer mortality among patients diagnosed with pneumoconiosis is increasing. Utilizing genome-wide sequencing technology, this study aimed to identify methods to decrease the number of patients with pneumoconiosis who die from lung cancer. METHODS: One hundred fifty-four subjects were recruited, including 54 pneumoconiosis patients and 100 healthy controls. Exosomes were isolated from the venous blood of every subject. Distinctive miRNAs were identified using high throughput sequencing technology, and bioinformatics analysis predicted target genes involved in lung cancer as well as their corresponding biological functions. Moreover, cross-cancer alterations of genes related to lung cancer were investigated, and survival analysis was performed using 2437 samples with an average follow-up period of 49 months. RESULTS: Let-7a-5p was revealed to be downregulated by 21.67% in pneumoconiosis. Out of the 683 let-7a-5p target genes identified from bioinformatics analysis, four genes related to five signaling pathways were confirmed to be involved in lung cancer development. Alterations in these four target genes were then explored in 4105 lung cancer patients, and BCL2L1 and IGF1R were demonstrated to be aberrantly expressed. Survival analysis further revealed that high expression of BCL2L1 corresponded to reduced survival of lung cancer patients (HR (95%CI) = 1.75(1.33~2.30)), while patient survival time was unaffected by expression of IGF1R (HR (95%CI) = 1.15 (0.98~1.36)). CONCLUSIONS: In patients with lung adenocarcinoma, simultaneous downregulation of exosomal let-7a-5p and elevated expression of BCL2L1 are useful as predictive biomarkers for poor survival.

Loss of regulatory characteristics in CD4+ CD25+/hi T cells induced by impaired transforming growth factor beta secretion in pneumoconiosis.

Pneumoconiosis is caused by the accumulation of airborne dust in the lung, which stimulates a progressive inflammatory response that ultimately results in lung fibrosis and respiratory failure. It is possible that regulatory cells in the immune system could function to suppress inflammation and possibly slow or reverse disease progression. However, results in this study suggest that in pneumoconiosis patients, the regulatory T cells (Tregs) and B cells are functionally impaired. First, we found that pneumoconiosis patients presented an upregulation of CD4+ CD25+ T cells compared to controls, whereas the CD4+ CD25+ and CD4+ CD25hi T cells were enriched with Th1- and Th17-like cells but not Foxp3-expressing Treg cells and evidenced by significantly higher T-bet, interferon (IFN)-γ, and interleukin (IL)-17 expression but lower Foxp3 and transforming growth factor (TGF)-ß expression. Regarding the CD4+ CD25hi T-cell subset, the frequency of this cell type in pneumoconiosis patients was significantly reduced compared to controls, together with a reduction in Foxp3 and TGF-ß and an enrichment in T-bet, RORγt, IFN-γ, and IL-17. This skewing toward Th1 and Th17 types of inflammation could be driven by monocytes and B cells, since after depleting CD14+ monocytes and CD19+ B cells, the levels of IFN-γ and IL-17 were significantly decreased. Whole peripheral blood mononuclear cells and isolated monocytes and B cells in pneumoconiosis patients also presented reduced capacity of TGF-ß secretion. Furthermore, monocytes and B cells from pneumoconiosis patients presented reduced capacity in inducing Foxp3 upregulation, a function that could be rescued by exogenous TGF-ß. Together, these data indicated a potential pathway for the progression of pneumoconiosis through a loss of Foxp3+ Treg cells associated with impaired TGF-ß secretion.

Association between Genetic Variants of Transforming Growth Factor-ß1 and Susceptibility of Pneumoconiosis: A Meta-analysis.

BACKGROUND: Transforming growth factor-beta 1 (TGF-ß1) and gene variants have been extensively studied in various human diseases. For example, TGF-ß1 polymorphisms were associated with fibrosis and pneumoconiosis, but the data remained controversial. The aim of this meta-analysis was to assess the association between TGF-ß1 -509 C>T [rs1800469], +869 T>C [rs1800470], and +915 G>C [rs1800471] polymorphisms and pneumoconiosis. METHODS: A comprehensive literature search was conducted through searching in PubMed, Embase, the Chinese Biomedical Database, and the Wei Pu (Chinese) Database by the end of April 2016. Eleven publications with 21 studies were included in this meta-analysis, covering a total of 4333 patients with pneumoconiosis and 3478 controls. Study quality was assessed, and heterogeneity and publication bias were measured. All statistical analyses were performed using STATA version 12.0 (StataCorp, College Station, TX, USA) software. RESULTS: The data showed significant associations between TGF-ß1 -509 C>T polymorphism and the risk of pneumoconiosis development (T vs. C, odds ratio [OR] = 1.35, 95% confidence interval [CI]: 1.00-1.81, P = 0.046); between TGF-ß1 +915 G>C polymorphism and the pneumoconiosis risk (C vs. G, OR = 1.69, 95% CI: 1.19-2.40, P = 0.004; CG vs. GG, OR = 1.79, 95% CI: 1.23-2.60, P = 0.002; CC+CG vs. GG, OR = 1.80, 95% CI: 1.24-2.61, P = 0.002). In addition, the subgroup analysis of ethnicity versus pneumoconiosis types indicated a significant association of silicosis among Asian populations but not that of coal workers' pneumoconiosis in Caucasian populations. In contrast, no significant association was exhibited between TGF-ß1 +869 T>C polymorphism and risk of pneumoconiosis. CONCLUSION: The polymorphisms of both TGF-ß1 -509 C>T and +915 G>C are associated with increased risk of pneumoconiosis.

[Preliminary study of exon sequence in pneumoconiosis and pneumoconiosis complicated with lung cancer using high-throughput sequencing technology].

Objective: The detection and analysis of exon mutations of pneumoconiosis and pneumoco-niosis complicated with lung cancer provide reference evidence for screening, clinical diagnosis and treatment and prognosis in pneumoconiosis and pneumoconiosis complicated with lung cancer. Methods: The pathologi-cal tissue samples from 3 pneumoconiosis patients and 3 pneumoconiosis complicated with lung cancer pa-tients were collected. Genomic DNA was extracted and library was prepared. Exomes of the pathological tissue samples in pneumoconiosis patients and pneumoconiosis complicated with lung cancer patients were se-quenced using Ion Torrent PGM platform. Results: Mutation genes FGFR3, PDGFRA, KDR, APC, EGFR, FGFR2, SMO, TP53, RET and CDKN2A were detected in pathological tissue samples of 3 pneumoconiosis patients; Mutation genes FGFR3, PDGFRA, KIT, KDR, APC, EGFR, FGFR2, TP53, RET, CDKN2A, ATM, NPM1, MET and FLT3 were detected in pathological tissue samples of 3 pneumoconiosis complicated with lung cancer patients (P<0.01) . FGFR3, PDGFRA were detected in pathological tissue samples of each pa-tient (mutation frequency>98%) ; Differential genes KIT, ATM, NPM1, MET and FLT3 were only detected in pathological tissue samples of pneumoconiosis complicated with lung cancer patients but not pneumoconio-sis patients. Conclusion: A variety of exon mutations detected in pneumoconiosis patients and pneumoconiosis complicated with lung cancer patients using high-throughput sequencing technique have potential value of ap-plications in screening, clinical diagnosis and treatment and prognosis in pneumoconiosis and pneumoconiosis complicated with lung cancer.

[Study of the association between interleukin-1 polymorphisms and genetic susceptibility of coal workers' pneumoconiosis and silicosis].

Objective: To evaluate the relationship between IL-1 gene polymorphisms and coal workers' pneumoconiosis and silicosis susceptibility. Methods: We searched published full-text from PubMed, Web of Science, CNKI, VIP and Wanfang to collect case-control study on IL-1 gene polymorphisms with coal workers' pneumoconiosis and silicosis susceptibility. Eight articles, including 10 case-control studies were included in our study. All analyses were performed using the Stata version 12.0 software. Results: The IL-1RA (+2018) TC or CC variant genotypes were associated with coal workers' pneumoconiosis and silicosis risk (OR=1.65, 95%CI: 1.11-2.46) . In further stratified analyses, the IL-1RA (+2018) TC or CC variant genotypes were associated with an increased silicosis risk (OR=2.07, 95%CI: 1.45-2.95) , which were also associated with increased coal workers' pneumoconiosis and silicosis risk in Caucasians (OR=1.74, 95%CI: 1.22-2.47) . No significant association between IL-1ß (+3953) , IL-1ß (-511) , IL-1α (+4845) and coal workers' pneumoconiosis and silicosis risk was found either in the overall study or in the stratified analysis. Conclusion: These findings suggested that IL-1RA (+2018) may modify coal workers' pneumoconiosis and silicosis susceptibility. Further replication studies with large sample sizes are warranted to re-evaluate the relationship between IL-1RA (+2018) and coal workers' pneumoconiosis and silicosis risk.

Forecasting role of genetic markers in outlining features of pneumoconiosis course in post-contact period.

Based on studies of certain gene-candidate polymorphism, the authors studied markers of early development and unfavorable course of pneumoconiosis in post-contact period. Analysis covered occurrence of genotypes and allels of I/D polymorphism of gene CCRS, 4a/b polymorphism of gene NOS3, VNTR polymorphism of gene ILRN, I/D polymorphism of CASP8 and mutation GLU342LYS (rs28929474) and GLU264VAL (rsl7S80) in gene SERPINAl in patients with various terms of pneumoconiosis formation. Findings are individual criteria of early formation and progress of pneumoconiosis in post-contact period..

Underground Coal Mining: Relationship between Coal Dust Levels and Pneumoconiosis, in Two Regions of Colombia, 2014.

In Colombia, coal miner pneumoconiosis is considered a public health problem due to its irreversibility, high cost on diagnosis, and lack of data related to its prevalence in the country. Therefore, a cross-sectional study was carried out in order to determine the prevalence of pneumoconiosis in underground coal mining workers in two regions of Colombia. The results showed a 35.9% prevalence of pneumoconiosis in the study group (42.3% in region 1 and 29.9% in region 2). An association was found between a radiologic diagnosis of pneumoconiosis and a medium risk level of exposure to carbon dust (OR: 2.901, 95% CI: 0.937, 8.982), medium size companies (OR: 2.301, 95% CI: 1.260-4.201), length of mining work greater than 25 years (OR: 3.222, 95% CI: 1.806-5.748), and a history of smoking for more than one year (OR: 1.479, 95% CI: 0.938-2.334). These results establish the need to generate an intervention strategy aimed at preventing the identified factors, as well as a timely identification and effective treatment of pneumoconiosis in coal miners, in which the commitment of the General Health and Social Security System and the workers compensation system is ensured.

A genome-wide association study identifies susceptibility loci of silica-related pneumoconiosis in Han Chinese.

Pneumoconiosis is the most serious occupational disease in China and its leading cause is occupational silica exposure. Pneumoconiosis takes several years to develop depending on the exposure level of silica. However, individual variation in the susceptibility to pneumoconiosis has been observed among the subjects with similar exposure. We conducted a genome-wide screening with 710,999 single nucleotide polymorphisms (SNPs) in a cohort of 400 coal workers (202 cases and 198 exposed controls) for pneumoconiosis susceptible loci. Seven promising variants were evaluated in an independent cohort of 568 coal workers (323 cases and 245 exposed controls), followed by a second replication on 463 iron ore workers (167 cases and 296 exposed controls). By pooling all of the genome-wide association studies and replication stages together, we found a genome-wide significant (P < 5.0 × 10(-8)) association for rs73329476 (P = 1.74 × 10(-8), OR = 2.17, 95% CI = 1.66-2.85) and two additional replicated associations for rs4320486 (P < 0.05) and rs117626015 (P < 0.05) with combined P-values of 4.29 × 10(-6) and 5.05 × 10(-6), respectively. In addition, the risk allele T of rs73329476 was significantly associated with lower mRNA expression levels of carboxypeptidase M (CPM) in total cellular RNA from whole blood of 156 healthy individuals (P = 0.0252). The identified pneumoconiosis susceptibility loci may provide new insights into the pathogenesis of pneumoconiosis, and may also have some clinical utility for risk prediction for pneumoconiosis and high-risk population screening for workers with occupational silica exposure.

Associations between tumor necrosis factor alpha gene -238 G/A and -308 G/A polymorphisms and the risk of pneumoconiosis: update of a meta-analysis.

OBJECTIVES: Tumor necrosis factor alpha (TNF-α) gene (-238 G/A [rs361525] and -308 G/A [rs1800629]) polymorphisms have been extensively studied in relation to various diseases, several epidemiologic studies have been performed to investigate the associations of TNF-α gene polymorphisms with pneumoconiosis; however, the results of these studies were not entirely consistent. In an effort to clarify earlier inconclusive results, we performed this meta-analysis of case-control genetic association studies. METHODS: We identified eligible studies by searching the relevant databases, including PubMed, Embase, Web of Science, CBMdisc, CNKI, and Google Scholar, until February 15, 2013. Additionally, hand searching of the references of identified articles were performed. Heterogeneity and publication bias across studies were determined and the meta-analysis was performed by Stata 11.0. RESULTS: Fourteen articles involving 20 studies were included in the final meta-analysis, covering a total of 1935 pneumoconiosis cases and 3753 controls. The results showed evidence for significant association between TNF-α gene -308 G/A polymorphism and pneumoconiosis risk, suggesting that TNF-α gene -308 A allele may be a risk factor for pneumoconiosis (for A allele vs. G allele: OR = 1.41, 95% CI = 1.10-1.81, p = 0.01; for A/A + G/A vs. G/G: OR = 1.52, 95% CI = 1.21-1.91, p < 0.01). For TNF-α gene -238 G/A polymorphism, no significant association was found between this genetic variation and pneumoconiosis risk. CONCLUSIONS: This meta-analysis indicates that TNF-α gene -308 G/A polymorphism is associated with an increased pneumoconiosis risk.

[Meta-analysis of association of tumor necrosis factor alpha and transforming growth factor beta gene polymorphisms with pneumoconiosis].

OBJECTIVE: To evaluate the relationship between tumor necrosis factor-alpha-238, transforming growth factor beta (509 and 869) gene polymorphisms and pneumoconiosis susceptibility. METHODS: We searched published full-text from foreign language databases including Elsevier, PubMed, Wiley Online Library, EMCC, Web of Science, chinese databases containing CNKI, VIP, Wanfang, CBM and Cochrane library to collect case-control or cohort study on gene gene polymorphisms said above with pneumoconiosis susceptibility from the year January1988 to August 2011. 28 relevant articles were selected and 20 of them met the criteria. The correlated index was extracted for aggregate analysis in RevMan 4.2. RESULTS: Among the 20 studies, 10 articles on TNF-α238 polymorphism (including 2232 pneumoconiosis cases and 1985 control subjects), 4 articles on TGF-ß509 polymorphism (including 693 pneumoconiosis cases and 663 control subjects), and 6 articles on TGF-ß869 polymorphism (including 1450 pneumoconiosis cases and 1101 control subjects) were included in the current study. Meta-analysis results showed that there was a significant association between TNF-α238 polymorphism and pneumoconiosis: the population with GA and AA genotypes of TNF-α238 had higher risks to pneumoconiosis (OR = 1.53, 95%CI: 1.25 ∼ 1.88) comparing to GG genotype, and the population with A allele had higher risks to pneumoconiosis comparing to allele G (OR = 1.64, 95%CI: 1.17 ∼ 2.30). The stratified analysis showed that the people with GA and AA genotypes and A allele who were silicosis, Asian or exposed to dust had higher risks to pneumoconiosis (OR = 2.14, 95%CI: 1.20 ∼ 3.82; OR = 2.16, 95%CI: 1.20 ∼ 3.88; OR = 1.78, 95%CI: 1.01 ∼ 3.11; OR = 1.83, 95%CI: 1.04 ∼ 3.22; OR = 1.80, 95%CI: 1.21 ∼ 2.66; OR = 1.50, 95%CI: 1.23 ∼ 1.83). No significant association was found between TGF-ß (509 and 869) gene polymorphisms with pneumoconiosis: In contrast to the CC genotype, the population who had CT and TT genotypes had no higher risks to pneumoconiosis (OR = 1.56, 95%CI: 0.81 ∼ 3.01; OR = 0.96, 95%CI: 0.79 ∼ 1.18); The population who had T allele had no higher risks to pneumoconiosis in contrast to the C allele (OR = 1.35, 95%CI: 0.86 ∼ 2.13; OR = 1.02, 95%CI: 0.91 ∼ 1.15). CONCLUSION: Significant association was found between TNFα238 gene polymorphism and pneumoconiosis; and TGF-ß (509 and 869) were not.

Interleukin gene polymorphisms in pneumoconiosis.

Inhaled asbestos fibres are known to cause inflammation processes with the result of lung or pleural fibrosis and malignancies. Interleukins (IL), such as IL-1ß, IL-6 and IL-10, have various functions in the regulation of the inflammatory response and in proliferative processes after inhalation of silica dust and can, therefore, influence the pathogenesis of asbestos-induced fibrosis and carcinogenesis. Polymorphisms within these genes may be associated with susceptibility to silica and asbestos-induced lung diseases. Thus, IL-1ß, IL-6 and IL-10 polymorphisms were examined to determine an association with asbestos or silica-induced fibrosis or malignancies. Association studies were performed in 1180 individuals, using control subjects (n=177), fibrosis patients (n=605), lung cancer (LC) patients (n=364) and malignant mesothelioma (MM) patients (n=34). IL-1ß (C-511T; C+3954T), IL-6 (G-174C) as well as IL-10 (G-1082A) polymorphisms were investigated. Compared to a healthy (control) group, a higher risk was seen for malignant mesothelioma patients in all investigated polymorphisms. The IL-6 -174C allele showed a tendency towards a higher risk for fibrosis or asbestos-induced lung cancer (ORasbestosis, 1.338; 95% CI, 0.71-2.53; ORsilicosis, 1.226; 95% CI, 0.54-2.81; ORfibrosis other aetiology, 1.313; 95% CI, 0.58-2.98 and ORLC asbestos, 2.112; 95% CI, 0.75-5.92). The IL-10 -1082A carrier seemed to be at higher risk for silicosis (ORsilicosis, 2.064; 95% CI, 0.78-5.49) but not for asbestosis. In summary, this study did not reveal sufficient evidence for a significant association of the investigated interleukin polymorphisms with asbestos or silica-induced diseases in the population studied.

[A meta-analysis of susceptibility to pneumoconiosis and polymorphism of tumor necrosis factor-α 308 and 238 locus].

OBJECTIVE: To explore the relationship between the polymorphism of TNF-α gene 308, 238 locus and the susceptibility to pneumoconiosis. METHODS: Eighteen published case-control studies about TNF-α gene 308, 238 locus polymorphism and pneumoconiosis susceptibility were searched out from sino-foreign databases from January 1994 to December 2010. Meta-analysis was applied on the published research to calculate the pooled OR value (95%CI) and stratified analyze the types and species of pneumoconiosis. RESULTS: Eleven of the published research articles were selected into the analysis, including 10 research focusing on TNF-α gene 308 locus, with 1408 cases and 1639 controls in total. The meta-analysis showed that comparing with Gln/Gln carriers, Arg/Arg, Arg/Gln, Gln/Arg + Arg/Arg carriers were 1.89-fold (95%CI: 1.10 - 3.24), 1.53-fold (95%CI: 1.25 - 1.87), and 1.56-fold (95%CI: 1.28 - 1.90) more susceptible to pneumoconiosis, respectively. The stratified analysis showed that among coal workers, the TNF-α gene 308 locus Arg/Arg, Arg/Gln, Gln/Arg + Arg/Arg carriers were separately 2.29-fold (95%CI: 1.22 - 4.29), 1.56-fold (95%CI: 1.20 - 2.03), 1.64-fold (95%CI: 1.28 - 2.11) more susceptible to pneumoconiosis than Gln/Gln carriers; and among Asian people, the TNF-α gene 308 locus Gln/Arg, Gln/Arg + Arg/Arg carriers were separately 1.58-fold (95%CI: 1.28 - 1.95) and 1.57-fold (95%CI: 1.28 - 1.94) more susceptible to pneumoconiosis than the Gln/Gln carriers. Four case-control research focus on the study of TNF-α gene 238 locus, including 391 cases and 391 controls in total. The analysis showed that comparing with the non-carriers, TNF-α gene 238 locus Arg/Arg, Arg/Gln, Gln/Arg + Arg/Arg carriers were 6.03-fold (95%CI: 1.35 - 26.97), 1.87-fold (95%CI: 1.07 - 3.30) and 2.36-fold (95%CI: 1.37 - 4.07) more susceptible to pneumoconiosis. CONCLUSION: TNF-α gene 308, 238 locus Arg/Arg, Gln/Arg, Gln/Arg + Arg/Arg carriers are more susceptible to pneumoconiosis.