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Susceptibility to progressive massive fibrosis (PMF) and polymorphisms in genes for antioxidant enzymes are not associated, according to the first case-control study to test this out. However, polymorphisms combined with environmental factors might still affect severity of the disease–a severe form of coal workers’ pneumoconiosis.
Common single polymorphic variants of glutathione S-transferase (GST) and manganese superoxide dismutase (MnSOD)—GSTP1, GSTT1, and MnSOD—were not statistically associated with PMF in 350 ex-underground coal workers compared with control miners matched for age, years of mining exposure, and smoking but with no evidence of lung fibrosis or inflammation. Nor were there any significant gene-gene interactions, which would be expected for a multifactorial disease like PMF. Frequencies of the polymorphisms conformed to the Hardy-Weinberg equilibrium in both groups. The study was powerful enough to detect a relation between susceptibility and polymorphic genes at an odds ratio of 1.8.
Histologically confirmed cases of PMF were identified from a well defined group of miners taking part in the national coal workers autopsy study in the United States during 1972–96, from whom necroscopic lung samples had been collected. Genetic analysis relied on DNA extracted and amplified from these samples.
Genes for antioxidant GSTs and superoxide dismutases MnSOD, which combat the harmful effects of reactive oxygen species in the lungs and help to protect against interstitial lung disease, are very polymorphic. Several common variants of GSTs have been associated with cancers of various organs, including lungs, and chronic obstructive pulmonary disease.
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