Promoter polymorphisms in glutathione-S-transferase genes affect transcription.
The glutathione-S-transferases are a group of enzymes that play a major role in detoxification and defence against toxic, carcinogenic and other compounds. We analysed the proximal promoters of 14 genes encoding glutathione-S-transferase for polymorphism. Ten of the promoters contained sequence variants, nine of which we were able to clone into a reporter gene vector, pGL3. The relative ability of each haplotype to promote transcription of the luciferase gene was tested in each of two human cell lines (HEK293t and TE671) using a cotransfected CMV-SEAP plasmid as a control. Four genes (GSTA1, GSTA2, GSTM4 and GSTT2) showed activity differences greater than 1.5-fold between haplotypes, and a fifth gene (MGST1) showed a 1.4-fold difference. The promoter sequence variants in these genes may therefore play a role in human variation, susceptibility to diseases and the effects of drugs.
Guy
Carol A
CA
Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, UK.
Hoogendoorn
Bastiaan
B
Smith
S Kaye
SK
Coleman
Sharon
S
O'Donovan
Michael C
MC
Buckland
Paul R
PR
D001483:Base Sequence; D020224:Expressed Sequence Tags; D017930:Genes, Reporter; D005982:Glutathione Transferase / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic / Q000235:genetics*
D005982:Glutathione Transferase