The glutathione S-transferase Θ and μ deletion polymorphisms in asbestosis

The glutathione S-transferases (GSTs) catalyze the conjugation of a wide variety of reactive electrophilic substrates with glutathione, facilitating their excretion. There is also evidence that GSTs can catalyze glutathione conjugation of lipid radicals as well as act in the generation of leukotriene inflammatory mediators. Studying construction carpenters screened for the presence of asbestos-related diseases, we have previously reported that the constitutional deletion of GSTMI (the gene coding, for glutathione S-tranferase class mu) associated with an increased risk of asbestos-related interstitial lung disease, measured radiographically. In the current work, we have further studied this group of worker investigating the distribution of a navel deletion polymorphism in the newly described GSTTI gene, that codes for the GST class theta enzyme. A total of 666 carpenters were studied, and 124 (19%) had the deleted genotype. There was no association between the GSTTI deletion and the radiographic diagnosis of either asbestos-related pleural or parenchymal disease. The GSTMI deletion remained associated with the presence of x-ray evidence asbestos after adjustment for GSTT1 genotype. The GSTM I null genotype was also associated with family history of any malignancy. These data suggest that the association of polymorphic GSTs with asbestos-induced radiographic changes is specific for substrates of the GST class mu.