Abstract
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 (ΔFEV1) = -152 ± 2.5 ml/year] and 322 nondecliners [ΔFEV1 = +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 105IIe/IIe 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 323-328 |
| Number of pages | 6 |
| Journal | American Journal of Respiratory and Critical Care Medicine |
| Volume | 166 |
| Issue number | 3 |
| DOIs | |
| State | Published - Aug 1 2002 |
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Keywords
- Forced expiratory volume
- Genetic predisposition to disease
- Obstructive lung diseases
Cite this
Antioxidant gene polymorphisms and susceptibility to a rapid decline in lung function in smokers. / He, Jian Qing; Ruan, Jian; Connett, John E; Anthonisen, Nicholas R.; Paré, Peter D.; Sandford, Andrew J.
In: American Journal of Respiratory and Critical Care Medicine, Vol. 166, No. 3, 01.08.2002, p. 323-328.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Antioxidant gene polymorphisms and susceptibility to a rapid decline in lung function in smokers
AU - He, Jian Qing
AU - Ruan, Jian
AU - Connett, John E
AU - Anthonisen, Nicholas R.
AU - Paré, Peter D.
AU - Sandford, Andrew J.
PY - 2002/8/1
Y1 - 2002/8/1
N2 - 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 (ΔFEV1) = -152 ± 2.5 ml/year] and 322 nondecliners [ΔFEV1 = +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 105IIe/IIe 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.
AB - 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 (ΔFEV1) = -152 ± 2.5 ml/year] and 322 nondecliners [ΔFEV1 = +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 105IIe/IIe 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.
KW - Forced expiratory volume
KW - Genetic predisposition to disease
KW - Obstructive lung diseases
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UR - http://www.scopus.com/inward/citedby.url?scp=0036683266&partnerID=8YFLogxK
U2 - 10.1164/rccm.2111059
DO - 10.1164/rccm.2111059
M3 - Article
C2 - 12153964
AN - SCOPUS:0036683266
VL - 166
SP - 323
EP - 328
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
SN - 1073-449X
IS - 3
ER -