Glutathione-S-transferase family of enzymes

The loci encoding the glutathione-S-transferase (GST) enzymes comprise a la rge supergene family located on at least seven chromosomes. The function of the GST enzymes has traditionally been considered to be the detoxication o f electrophiles by glutathione conjugation. A wide variety of endogenous (e .g. by-products of reactive oxygen species activity) and exogenous (e.g. po lycyclic aromatic hydrocarbons) electrophilic substrates have been identifi ed. Interestingly, recent data has suggested a role, at least for the pi cl ass gene product, in jun kinase inhibition. Since many GST genes are polymo rphic, there has been considerable interest in determining whether particul ar allelic variants are associated with altered risk (or outcome) of a vari ety of diseases. We describe recent studies in patients with asthma and cut aneous basal cell carcinoma that demonstrate associations between GSTP1 and GSTT1 genotypes and disease phenotypes. Thus, GSTP1val(105)/val(105) was p rotective against asthma symptoms and GSTT1 null was associated with a subg roup of basal cell carcinoma patients who develop large numbers of primary tumours in clusters. Importantly, these associations were characterised by relatively large odds ratios (0.11 and 7.4, respectively) implying that the allelic variants exert a substantial biological effect. These and other da ta indicate the importance of GST polymorphism in determining disease pheno type. (C) 2001 Elsevier Science B.V. All rights reserved.