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Genetic risk factors in progressive massive fibrosis in coal miners.

Authors
Yucesoy-B; Johnson-VJ; Fluharty-K; Kashon-ML; Slaven-J; Kissling-G; Germolec-D; Vallyathan-V; Luster-MI
Source
Toxicologist 2008 Mar; 102(1):83
NIOSHTIC No.
20033547
Abstract
Progressive massive fibrosis (PMF) is a chronic interstitial lung disease with a complex etiology. Cytokines, growth factors and cell-surface adhesion molecules play crucial roles in the pathogenesis of pulmonary fibrosis by mediating inflammation, fibroblast proliferation, angiogenesis, and collagen synthesis. 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 with demographic information submitted to the National Coal Workers Autopsy Study (NCWAS). SNPs, which influence the regulation of interleukin-1 (IL-1), IL-6, tumor necrosis factor-alpha (TNF-alpha), transforming growth factor beta-1 (TGF-alpha1), vascular endothelial growth factor (VEGF), intercellular cell adhesion molecule-1 (ICAM-1), and matrix metalloproteinase-2 (MMP-2) genes, were determined using a 5'-nuclease real-time PCR assay from autopsy lung tissue DNA. 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 +241/-IL6 -174 (C-A-G) conferred an increased risk for PMF. These data suggest that single variants of cytokine and fibrogenic genes are unlikely to strongly influence susceptibility to PMF, although the role of VEGF, ICAM-1, and IL-6 polymorphisms in the development of PMF may require further investigation.
Keywords
Cell-biology; Cell-transformation; Cellular-reactions; Cell-alteration; Pathogenicity; Pathogens; Pathomorphology; Molecular-biology; Molecular-structure; Pulmonary-system-disorders; Lung-fibrosis; Lung-irritants; Lung-disease; Lung-cells; Coal-dust; Coal-miners; Coal-processing; Coal-workers-pneumoconiosis; Fibrogenicity; Fibrous-bodies; Fibrous-dusts
Publication Date
20080301
Document Type
Abstract
Fiscal Year
2008
NTIS Accession No.
NTIS Price
Issue of Publication
1
ISSN
1096-6080
NIOSH Division
HELD
Source Name
The Toxicologist. Society of Toxicology 47th Annual Meeting and ToxExpo, March 16-20, 2008, Seattle, Washington
State
WV; WA
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