Genetic susceptibility to progressive massive fibrosis in coal miners

¹ Toxicology and Molecular Biology
² Biostatistics
³ Biostatistics and Epidemiology
⁴ Toxicology Operations Branches, NIEHS, Research Triangle Park, NC
⁵ Pathology and Physiology Research Branches, CDC/NIOSH, Morgantown, WV

^* To whom correspondence should be addressed. E-mail: mailto:byucesoy{at}cdc.gov.

	Abstract

Progressive massive fibrosis (PMF) is a chronic interstitial lung disease with a complex etiology that can occur from 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 (NCWAS) of which 304 were diagnosed with PMF. SNPs, which influence the regulation of interleukin-1 (IL-1), IL-6, tumour necrosis factor-alpha (TNF), transforming growth factor beta-1 (TGF1), 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.

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 (OR=3.4, CI: 1.3–8.8).

This 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 VEGF, ICAM-1 and IL-6 polymorphisms in the development of PMF may require further investigation.