Genetic variation in TGF-beta1 but not antioxidant genes is associated with progressive massive fibrosis in coal workers.
Yucesoy-B; Johnson-VJ; Kashon-ML; Fluharty-K; Willard-P; Vallyathan-V; Luster-MI
Toxicologist 2004 Mar; 78(S-1):422-423
Progressive massive fibrosis (PMF) is the severe form of coal worker's pneumoconiosis. Although the severity of PMF is mostly dependent on the total amount and duration of dust exposure, genetic factors also play an important role in the development of disease and modify the individual susceptibility. Studies have implicated reactive oxygen species (ROS) in the pathogenesis of fibrosis and other lung diseases. Many chemicals and physical agents including mineral dusts are potent generators of ROS. Lung tissue is protected against ROS by a variety of antioxidant mechanisms such as superoxide dismutases (SOD) and glutathione s-transferases (GSTs). Transforming growth factor beta (TGB ) is a key profibrotic growth factor implicated in fibrosis, including the deposition of extracellular matrix proteins. Antioxidant enzyme and cytokine genes are subject to polymorphisms in their regulatory regions which affect their expression level and thus contribution to disease process. This study was undertaken to examine the association between the functional polymorphisms of TGB and antioxidant enzyme genes and progression of PMF as well as possible gene-gene and gene-environment interactions. We genotyped DNA collected from lung autopsy tissues from 270 miners diagnosed with PMF as well as in 270 control miners with no disease using a case-control study design. Polymorphisms in GSTP1, GSTM1, GSTT1, MnSOD and TGB were analyzed by Taqman assay to determine each genotype. Our results showed an association of PMF prevalence with TGB 1 (-509) TT genotype (OR 1.77; 95% CI 1.03-3.09), whereas no statistically significant differences in the allele frequencies of antioxidant genes were observed between the cases and controls. The results suggest that interactions of genetic background with environmental exposure may affect the pathogenesis of PMF.
Genetic-factors; Genes; Antioxidants; Fibrosis; Coal-miners; Pneumoconiosis; Dust-exposure; Diseases; Lung-disease; Pulmonary-system-disorders; Respiratory-system-disorders; Mineral-dusts; Lung-tissue; Environmental-exposure; Pathogenesis
Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
The Toxicologist. Society of Toxicology 43nd Annual Meeting and ToxExpo, March 21-25, 2004, Baltimore, Maryland