Molecular genetics of the human glutathione S-transferase

Abstract

Multiple human cytosolic glutathione transferases have been described. These enzymes are the products of multiple genes that can be classified into at least four evolutionary classes. The genes encoding each class appear to be clustered on distinct chromosomes. Over-expression of glutathione S-transferase (GST) isoenzymes has been implicated in drug resistance and, conversely, deficiency of GST isoenzymes has been implicated in susceptibility to carcinogens. Some GST genes are expressed at varying levels in different individuals, and there is a frequent deficiency of the Mu class GST1 isoenzyme in all the racial groups studied so far. This deficiency is due to a deletion of the GST 1 gene. The Alpha class genes are located on the short arm of chromosome 6 and are closely linked, with less than 2 kb separating some genes. There is evidence for the existence of several pseudogenes in this cluster. A complete Alpha class gene has 7 exons and extends over 13 kb. The 5' flanking region of the gene encoding the GST2 type 1 isoenzyme has been cloned and sequenced. This region contains a number of putative promoter and enhancer elements that are similar to those found in rat and mouse Alpha class genes.