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.
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 COPDpatients 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 COPDpatients. 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: Charlie Strange; Robert M Senior; Frank Sciurba; Scott O'Neal; Alison Morris; Stephen R Wisniewski; Russell Bowler; Harry S Hochheiser; Michael J Becich; Yingze Zhang; Joseph K Leader; Barbara A Methé; Naftali Kaminski; Robert A Sandhaus Journal: Ann Am Thorac Soc Date: 2015-10
Authors: Dawn L Demeo; Edward J Campbell; Alan F Barker; Mark L Brantly; Edward Eden; N Gerard McElvaney; Stephen I Rennard; Robert A Sandhaus; James M Stocks; James K Stoller; Charlie Strange; Gerard Turino; Edwin K Silverman Journal: Am J Respir Cell Mol Biol Date: 2007-08-09 Impact factor: 6.914
Authors: P J Castaldi; D L DeMeo; D M Kent; E J Campbell; A F Barker; M L Brantly; E Eden; N G McElvaney; S I Rennard; J M Stocks; J K Stoller; C Strange; G Turino; R A Sandhaus; J L Griffith; E K Silverman Journal: Am J Epidemiol Date: 2009-09-02 Impact factor: 4.897
Authors: Woo Jin Kim; Alice M Wood; Alan F Barker; Mark L Brantly; Edward J Campbell; Edward Eden; Gerard McElvaney; Stephen I Rennard; Robert A Sandhaus; James M Stocks; James K Stoller; Charlie Strange; Gerard Turino; Edwin K Silverman; Robert A Stockley; Dawn L Demeo Journal: Respir Res Date: 2012-02-22