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Updated: Jun 4, 2026
14:57
Spectrophotometric Screening for Potential Inhibitors of Cytosolic Glutathione S-Transferases
Published on: October 10, 2020
Glutathione S-transferase copy number variation alters lung gene expression
M W Butler1, N R Hackett, J Salit
1Dept of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
The European Respiratory Journal
|February 26, 2011
Summary
Germline copy number variations (CNVs) impact glutathione S-transferase (GST) gene expression in lung cells. This suggests GST gene polymorphisms may increase the risk of smoking-related lung diseases.
Area of Science:
- Toxicology
- Genetics
- Pulmonology
Background:
- Glutathione S-transferase (GST) enzymes detoxify xenobiotics.
- Inherited copy number variations (CNVs) can alter GST gene expression.
- Small airway epithelium (SAE) and alveolar macrophages (AMs) are key in early smoking-induced lung disease.
Purpose of the Study:
- To investigate if germline CNVs influence GST gene expression levels in SAE and AMs.
- To determine the relationship between GST gene CNVs and their expression in lung tissues of smokers and nonsmokers.
Main Methods:
- Gene expression and CNV genotyping were analyzed using microarrays.
- SAE and AMs were collected via bronchoscopy from smokers and nonsmokers.
- Specific GST genes (GSTM1, GSTT1, GSTT2B) were examined for CNVs and mRNA levels.
Main Results:
- 26% of subjects had GSTM1 null genotypes, showing reduced GSTM1 mRNA in SAE and AMs.
- 30% of subjects had GSTT1 homozygous deletions, with decreased GSTT1 mRNA in both tissues.
- GSTT2B deletions were observed in 27% of subjects; expression in AMs correlated with genotype.
Conclusions:
- Germline CNVs directly influence GST gene expression levels in SAE and AMs.
- Minimal compensatory expression was observed in heterozygotes.
- GST gene polymorphisms, influenced by CNVs, likely contribute to smoking-associated lung disease risk.
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