Genetic susceptibility to progressive massive fibrosis in coal miners.
Yucesoy B; Johnson VJ; Kissling GE; Fluharty K; Kashon ML; Slaven J; Germolec D; Vallyathan V; Luster MI
Eur Respir J 2008 Jun; 31(6):1177-1182
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-ß1, 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.
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
B. Yucesoy, Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, WV 26505-2888, USA
European Respiratory Journal