Glutathione S-transferase P1 and lung function in patients with alpha1-antitrypsin deficiency and COPD

Chest. 2005 May;127(5):1537-43. doi: 10.1378/chest.127.5.1537.


Background: The glutathione S-transferase P1 (GSTP1) gene is involved in detoxification of electrophilic substances of tobacco smoke. A polymorphism at nucleotide 315 of this gene alters its enzymatic activity.

Objective: We analyzed the association between the variability in the GSTP1 gene and impairment in lung function in smokers with and without alpha(1)-antitrypsin (AAT) deficiency and COPD.

Population and method: The study population consisted of 99 patients with smoking-related COPD and 69 patients with AAT deficiency; 198 healthy volunteers provided the frequency of the different polymorphisms in the general population. GSTP1 genotyping was performed by a real-time polymerase chain reaction amplification assay.

Results: The frequency (0.28) of the 105Val polymorphism was identical in COPD patients and the general population. However, the frequency was significantly increased (0.44) in patients with AAT deficiency (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.17 to 3.72 compared to control subjects; and OR, 2.41; 95% CI, 1.27 to 4.59 compared to COPD). FEV(1) percentage of predicted was significantly impaired in AAT-deficient carriers of 105Val. This effect was not observed in COPD patients.

Conclusions: These findings suggest that the frequency of the GSTP1 105Val polymorphism is increased in patients with AAT deficiency. Globally, GSTP1 genotypes, age, and tobacco smoking explained 41% of total FEV(1) percentage of predicted variability in patients with AAT deficiency. The modulatory role of GSTP1 in lung disease has only been observed in smokers lacking AAT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Female
  • Forced Expiratory Volume
  • Genotype
  • Glutathione S-Transferase pi
  • Glutathione Transferase / genetics*
  • Humans
  • Isoenzymes / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Pulmonary Disease, Chronic Obstructive / genetics*
  • Smoking / genetics*
  • Valine / genetics
  • alpha 1-Antitrypsin Deficiency / genetics*


  • Isoenzymes
  • GSTP1 protein, human
  • Glutathione S-Transferase pi
  • Glutathione Transferase
  • Valine