THE GLUTATHIONE-S-TRANSFERASE THETA-DELETION AND MU-DELETION POLYMORPHISMS IN ASBESTOSIS

The glutathione S-transferases (GSTs) catalyze the conjugation of a wi de variety of reactive, electrophilic substrates with glutathione, fac ilitating their excretion. There is also evidence that GSTs can cataly ze glutathione conjugation of lipid radicals as well as act in the gen eration of leukotriene inflammatory mediators. Studying construction c arpenters screened for the presence of asbestos-related diseases, we h ave previously reported that the constitutional deletion of GSTM1 (the gene coding for glutathione S-transferase class mu) is associated wit h an increased risk of asbestos-related interstitial lung disease, mea sured radiographically. In the current work, we have further studied t his group of workers, investigating the distribution of a novel deleti on polymorphism in the newly described GSTT1 gene, that codes for the GST class theta enzyme. A total of 666 carpenters were studied, and 12 4 (19%) had the deleted genotype. There was no association between the GSTT1 deletion and the radiographic diagnosis of either asbestos-rela ted pleural or parenchymal disease. The GSTM1 deletion remained associ ated with the presence of x-ray evidence of asbestosis after adjustmen t for GSTT1 genotype. The GSTM1 null genotype was also associated with a family history of any malignancy. These data suggest that the assoc iation of polymorphic GSTs with asbestos-induced radiographic changes is specific for substrates of the GST class mu. (C) 1997 Wiley-Liss, I nc.