TY - JOUR
T1 - Glutathione S-transferase variants and their interaction with smoking on lung function
AU - He, Jian Qing
AU - Connett, John E.
AU - Anthonisen, Nicholas R.
AU - Paré, Peter D.
AU - Sandford, Andrew J.
PY - 2004/8/15
Y1 - 2004/8/15
N2 - We studied glutathione S-transferase (GST) polymorphisms in 1,098 whites with the lowest (n = 544, FEV1 % predicted mean ± SEM = 62.6 ± 0.1) and the highest (n = 554, FEV1 % predicted mean ± SEM = 91.8 ± 0.1) lung function at the beginning of the Lung Health Study. Homozygosity for GSTP1 105Val was significantly more frequent in the low- than in the high-function group (13.2 vs. 9.3%) (odds ratio = 1.69, 95% confidence interval [CI] = 1.11-2.61, p = 0.016), after adjustment for confounding variables. Subjects with 105Val homozygotes had higher rates of lung function decline in the high-function group (p = 0.017). The frequencies of GSTM1, GSTT1 null genotypes were similar between the high- and low-function groups, but subjects with the GSTT1 null genotype had a faster decline of lung function in the low-function group (p = 0.032). In addition, there was a significant interaction of GSTT1 genotype and pack-years on lung function. When comparing individuals with GSTT1 null genotype with wild type, the adjusted odds ratio was 3.49 (95% CI, 1.48-8.39, p = 0.005) in mild smokers (≤ 25 pack years). We conclude that GST genotypes are risk factors for rapid decline or low lung function in smokers with mild to moderate airflow obstruction.
AB - We studied glutathione S-transferase (GST) polymorphisms in 1,098 whites with the lowest (n = 544, FEV1 % predicted mean ± SEM = 62.6 ± 0.1) and the highest (n = 554, FEV1 % predicted mean ± SEM = 91.8 ± 0.1) lung function at the beginning of the Lung Health Study. Homozygosity for GSTP1 105Val was significantly more frequent in the low- than in the high-function group (13.2 vs. 9.3%) (odds ratio = 1.69, 95% confidence interval [CI] = 1.11-2.61, p = 0.016), after adjustment for confounding variables. Subjects with 105Val homozygotes had higher rates of lung function decline in the high-function group (p = 0.017). The frequencies of GSTM1, GSTT1 null genotypes were similar between the high- and low-function groups, but subjects with the GSTT1 null genotype had a faster decline of lung function in the low-function group (p = 0.032). In addition, there was a significant interaction of GSTT1 genotype and pack-years on lung function. When comparing individuals with GSTT1 null genotype with wild type, the adjusted odds ratio was 3.49 (95% CI, 1.48-8.39, p = 0.005) in mild smokers (≤ 25 pack years). We conclude that GST genotypes are risk factors for rapid decline or low lung function in smokers with mild to moderate airflow obstruction.
KW - Cigarette smoking
KW - FEV
KW - Gene-environment interaction
KW - Genetic polymorphism
KW - Glutathione S-transferase
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U2 - 10.1164/rccm.200312-1763OC
DO - 10.1164/rccm.200312-1763OC
M3 - Article
C2 - 15184197
AN - SCOPUS:4544264842
SN - 1073-449X
VL - 170
SP - 388
EP - 394
JO - American journal of respiratory and critical care medicine
JF - American journal of respiratory and critical care medicine
IS - 4
ER -