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Promoter polymorphisms in glutathione-S-transferase genes affect transcription

Guy, Carol A; Hoogendoorn, Bastiaan; Smith, S Kaye; Coleman, Sharon; O'Donovan, Michael C; Buckland, Paul R

Original Articles

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.

Author Information

Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, UK.

Correspondence and requests for reprints to Paul Buckland, Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, UK Tel: +44 (0) 2920 744840; fax: +44 (0) 2920 747839; e-mail:

Received 28 May 2003 Accepted 18 October 2003

© 2004 Lippincott Williams & Wilkins, Inc.