Genetic susceptibility to progressive massive fibrosis in coal miners

Toxicology and Molecular Biology Branch, Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health, Morgantown, WV 26505-2888, USA.
European Respiratory Journal (Impact Factor: 7.13). 07/2008; 31(6):1177-82. DOI: 10.1183/09031936.00075107
Source: PubMed

ABSTRACT Progressive massive fibrosis (PMF) is a chronic interstitial lung disease with a complex aetiology that can occur after cumulative dust exposure. A case-control study was conducted to test the hypothesis that single nucleotide polymorphisms (SNPs) within genes involved in inflammatory and fibrotic processes modulate the risk of PMF development. The study population consisted of 648 underground coal miners participating in the National Coal Workers Autopsy Study, of which 304 were diagnosed with PMF. SNPs that influence the regulation of interleukin (IL)-1, IL-6, tumour necrosis factor-alpha, transforming growth factor-beta1, vascular endothelial growth factor (VEGF), epidermal growth factor intercellular cell adhesion molecule (ICAM)-1 and matrix metalloproteinase-2 genes were determined using a 5'-nuclease real-time PCR assay. There were no significant differences in the distribution of any individual SNP or haplotype between the PMF and control groups. However, the polygenotype of VEGF +405/ICAM-1 +241/IL-6 -174 (C-A-G) conferred an increased risk for PMF (odds ratio 3.4, 95% confidence interval 1.3-8.8). The present study suggests that the examined genetic variations that help regulate inflammatory and fibrotic processes are unlikely to strongly influence susceptibility to this interstitial lung disease, although the role of vascular endothelial growth factor, intercellular cell adhesion molecule-1 and interleukin-6 polymorphisms in the development of progressive massive fibrosis may require further investigation.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this case-control study was to explore whether five tagging single nucleotide polymorphisms (tSNPs) within the transforming growth factor-β1 (TGF-β1) gene were involved in manifestation of inflammatory and fibrotic processes associated with coal workers' pneumoconiosis (CWP). The study included 508 CWP patients and 526 controls who were underground coal miners from Xuzhou Mining Business Group. Five tSNPs were selected from the HapMap and detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The single SNP analysis showed that the genotype frequencies of SNP2 (rs1800470, +869T/C, extron 1) and SNP5 (rs11466345, intron 5) in CWP cases were significantly different from those in controls. Multivariate logistic regression analysis revealed that SNP2 (rs1800470) CC genotype was associated with decreased risk of CWP (OR = 0.50, 95% CI = 0.32-0.78), which was evident among subgroups of those never smoke (OR = 0.40, 95%CI = 0.24-0.66), cases with stage II (OR = 0.41, 95%CI = 0.22-0.76) and exposure period (< 28 y: OR = 0.54, 95%CI = 0.31-0.95; ≥28 y: OR = 0.52, 95%CI = 0.32-0.96). However, the SNP5 (rs11466345) GG genotype was associated with an increased risk of CWP (OR = 2.5, 95%CI = 1.36-4.57), and further stratification analysis showed that the risk of CWP was increased in both smoking and nonsmoking groups, shorter and longer exposure groups, while the risk of CWP was only increased in patients with stage I and II. This study suggests that TGF-β1 polymorphisms may contribute to susceptibility of CWP.
    07/2010; 24(4):270-6. DOI:10.1016/S1674-8301(10)60038-3
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract 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 = 0.00). 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.
    Current Medical Research and Opinion 08/2013; DOI:10.1185/03007995.2013.831817 · 2.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Coal mining remains a sizable industry, with millions of working and retired coal miners worldwide. This article provides an update on recent advances in the understanding of respiratory health issues in coal miners and focuses on the spectrum of disease caused by inhalation of coal mine dust, termed coal mine dust lung disease (CMDLD). In addition to the historical interstitial lung diseases (coal worker's pneumoconiosis, silicosis, and mixed dust pneumoconiosis), coal miners are at risk for dust-related diffuse fibrosis (DDF) and chronic airway diseases including emphysema and chronic bronchitis. Recent recognition of rapidly progressive pneumoconiosis in younger miners, mainly in the eastern United States, has increased the sense of urgency and the need for vigilance in medical research, clinical diagnosis, and exposure prevention. Given the risk for disease progression even after exposure removal, along with few medical treatment options, there is an important role for chest physicians in the recognition and management of lung disease associated with work in coal mining.
    American Journal of Respiratory and Critical Care Medicine 04/2013; DOI:10.1164/rccm.201301-0042CI · 11.99 Impact Factor

Full-text (2 Sources)

Available from
May 17, 2014