Glutathione-S-transferase family of enzymes.
The loci encoding the glutathione-S-transferase (GST) enzymes comprise a large supergene family located on at least seven chromosomes. The function of the GST enzymes has traditionally been considered to be the detoxication of electrophiles by glutathione conjugation. A wide variety of endogenous (e.g. by-products of reactive oxygen species activity) and exogenous (e.g. polycyclic aromatic hydrocarbons) electrophilic substrates have been identified. Interestingly, recent data has suggested a role, at least for the pi class gene product, in jun kinase inhibition. Since many GST genes are polymorphic, there has been considerable interest in determining whether particular allelic variants are associated with altered risk (or outcome) of a variety of diseases. We describe recent studies in patients with asthma and cutaneous basal cell carcinoma that demonstrate associations between GSTP1 and GSTT1 genotypes and disease phenotypes. Thus, GSTP1val(105)/val(105) was protective against asthma symptoms and GSTT1 null was associated with a subgroup 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 data indicate the importance of GST polymorphism in determining disease phenotype.
Strange
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RC
Centre for Cell and Molecular Medicine, School of Postgraduate Medicine, Keele University, North Staffordshire Hospital, Stoke-on-Trent, Staffordshire, UK. paa00@keele.ac.uk
Spiteri
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MA
Ramachandran
S
S
Fryer
A A
AA
D001249:Asthma / Q000235:genetics*; D002280:Basal Cell Carcinoma / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D011110:Polymorphism, Genetic; D012878:Skin Neoplasms / Q000235:genetics*
D007527:Isoenzymes; C407705:GSTZ1 protein, human; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase