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American Journal of Respiratory and Critical Care Medicine Vol 166. pp. 323-328, (2002)
© 2002 American Thoracic Society

Original Article

Antioxidant Gene Polymorphisms and Susceptibility to a Rapid Decline in Lung Function in Smokers

Jian-Qing He, Jian Ruan, John E. Connett, Nicholas R. Anthonisen, Peter D. Paré and Andrew J. Sandford

UBC McDonald Research Laboratories/iCAPTURE Center, St. Paul's Hospital, Vancouver, British Columbia, Canada; Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota; and Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada

Correspondence and requests for reprints should be addressed to Dr. A. J. Sandford, UBC McDonald Research Laboratories/iCAPTURE Center, St. Paul's Hospital, 1081 Burrard Street, Vancouver, BC, V6Z 1Y6 Canada. E-mail: asandford{at}mrl.ubc.ca

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 ({Delta}FEV1) = -152 ± 2.5 ml/year] and 322 nondecliners [{Delta}FEV1 = +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.

Key Words: obstructive lung diseases • forced expiratory volume • genetic predisposition to disease




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