Promoter polymorphisms in glutathione-S-transferase genes affect transcription

Pharmacogenetics. 2004 Jan;14(1):45-51. doi: 10.1097/00008571-200401000-00005.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Expressed Sequence Tags
  • Genes, Reporter
  • Glutathione Transferase / genetics*
  • Haplotypes
  • Humans
  • Promoter Regions, Genetic*
  • Transcription, Genetic / genetics*

Substances

  • Glutathione Transferase