Genetic susceptibility to progressive massive fibrosis in coal miners

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-a, transforming growth factor-b1, vascular endothelial growth factor (VEGF), epidermal growth factor intercellular cell adhesion molecule (ICAM)-1 and matrix metalloproteinase-2 genes were determined using a 59-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.

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

“…Of these, 562 articles were excluded based on the inclusion criteria. Finally, 14 articles involving 20 studies met the inclusion criteria and were included in the final meta-analysis [10][11][12][13][14][15][16][17][18][19][20][21][22][23] . The data were gathered from a total of 1935 pneumoconiosis cases and 3753 controls.…”

“…The data were gathered from a total of 1935 pneumoconiosis cases and 3753 controls. Six of these studies investigated the association between TNF-a gene -238 G/A polymorphism and pneumoconiosis 10,12,15,17,18,22 , and 14 studies involved TNF-a gene -308 G/A polymorphism [10][11][12][13][14][15][16][17][18][19][20][21][22][23] . Table 1 shows the studies identified and their main characteristics.…”

“…Previous studies have reported that TNF-a is associated with the toxic and pathogenic effects observed in humans or animals exposed to mineral dusts such as silica and coal dust [7][8][9] . Furthermore, associations of TNF-a gene (-238 G/A [rs361525] and -308 G/A [rs1800629]) polymorphisms and the risk of pneumoconiosis have also been widely studied but the results were somewhat conflicting [10][11][12][13][14][15][16][17][18][19][20][21][22][23] . In 2002, Corbett et al found that TNF-a gene -238 A allele and -308 A allele were associated with an increased risk of the severe silicosis among black South African miners 10 .…”

“…However, they also demonstrated that TNF-a gene -238 G/A polymorphism was not association with CWP risk. In 2008, Yucesoy et al also showed that there was no significant association between TNF-a gene -238 G/A and -308 G/A polymorphisms and progressive massive fibrosis (PMF) of the lung among coal miners in America 18 . In addition to the above studies, Ates et al found that TNF-a gene -238 A allele was associated with an increased CWP risk among Turks in 2011 22 .…”

Individual Susceptibility to Occupational Hazard

“…For workers exposed to asbestos, it is suggested that GSTP1*105Val allele and low EPHX1 activity genotype (glutathione S-transferases and microsomal epoxide hydrolase, respectively) are protective 5) . Yucesoy et al 6) conducted a case-control study to test the hypothesis that the polymorphisms within genes involved in inflammatory and fibrotic processes modulate the risk of progressive massive fibrosis among underground coal miners, and observed that the polygenotype of VEGF +405/ICAM-1 +241/IL-6 -174 (C-A-G) conferred an increased risk for PMF (VEGF = vascular endothelial growth factor and ICAM = epidermal growth factor intercellular cell adhesion molecule). The susceptibility, of course, must be concern in non-occupational exposures, as reported by Liao YT et al 7) that residents in Taiwan exposed to high levels of arsenic (cumulative exposure >14.7 ppm-year or drinking artesian well water >21 yr) and carrying the R-C-S haplotype (constituted by polymorphisms of paraoxonase genes PON1 Q192R, -108C/T and PON2 C311S) were associated with the incidence of electrocardiogram abnormality.…”