title: Glutathione S-transferase P1 and lung function in patients with alpha1-antitrypsin deficiency and COPD.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Department of Biochemistry, Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Rodriguez
authors.forename: Cristian
authors.initials: C
authors.lastname: de la Roza
authors.forename: Rosendo
authors.initials: R
authors.lastname: Jardi
authors.forename: Melanie
authors.initials: M
authors.lastname: Schaper
authors.forename: Rafael
authors.initials: R
authors.lastname: Vidal
authors.forename: Marc
authors.initials: M
authors.lastname: Miravitlles
mesh_terms: D000368:Aged; D005260:Female; D005541:Forced Expiratory Volume; D005838:Genotype; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics*; D012907:Smoking / Q000235:genetics*; D014633:Valine / Q000235:genetics; D019896:alpha 1-Antitrypsin Deficiency / Q000235:genetics*
chemical_list: D007527:Isoenzymes; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D014633:Valine