Antioxidant gene polymorphisms and susceptibility to a rapid decline in lung function in smokers.
Oxidative stress is believed to play an important role in the pathogenesis of smoking-induced chronic obstructive pulmonary disease. We hypothesized that polymorphisms of antioxidant genes glutathione S-transferase M1 (GSTM1), GSTT1, GSTP1, and heme oxygenase-1 (HMOX1) would be associated with susceptibility to accelerated decline of lung function in smokers. We genotyped 621 subjects (299 rapid decliners [change in forced expiratory volume in 1 second (DeltaFEV(1)) = -152 +/- 2.5 ml/year] and 322 nondecliners [DeltaFEV(1) = +15 +/- 1.5 ml/year]) selected from among smokers followed for 5 years in the National Heart, Lung, and Blood Institute Lung Health Study. Because genotype frequencies were different between ethnic groups, we limited the association study to 594 whites (286 rapid decliners and 308 nondecliners). None of the genotypes studied had a statistically significant effect on decline of lung function when analyzed separately. There was an association between rapid decline of lung function and presence of all three GST polymorphisms (odds ratio [OR] = 2.83; p = 0.03). A combination of a family history of chronic obstructive pulmonary disease with GSTP1 105Ile/Ile genotype was also associated with rapid decline of lung function (OR = 2.20; p = 0.01). However, due to the multiple comparisons that were made, these associations may represent type 1 error. There was no association between HMOX1 (GT)n alleles and the rate of decline in lung function in smokers.
He
Jian-Qing
JQ
UBC McDonald Research Laboratories/iCAPTURE Center, St. Paul's Hospital, 1081 Burrard Street, Vancouver, British Columbia, V6Z 1Y6 Canada.
Ruan
Jian
J
Connett
John E
JE
Anthonisen
Nicholas R
NR
Paré
Peter D
PD
Sandford
Andrew J
AJ
D000328:Adult; D005260:Female; D005541:Forced Expiratory Volume / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics*; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D051547:Heme Oxygenase-1; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008171:Lung Diseases / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012129:Respiratory Function Tests; D012907:Smoking / Q000235:genetics*; D013997:Time Factors
D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D007527:Isoenzymes; D008565:Membrane Proteins; C496541:HMOX1 protein, human; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human