Glutathione S-transferase variants and their interaction with smoking on lung function.
We studied glutathione S-transferase (GST) polymorphisms in 1,098 whites with the lowest (n = 544, FEV(1) % predicted mean +/- SEM = 62.6 +/- 0.1) and the highest (n = 554, FEV(1) % 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 (< or = 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.
He
Jian-Qing
JQ
The James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, St. Paul's Hospital, 1081 Burrard Street, Vancouver, BC V6Z 1Y6, Canada.
Connett
John E
JE
Anthonisen
Nicholas R
NR
Paré
Peter D
PD
Sandford
Andrew J
AJ
D000217:Acyltransferases / Q000235:genetics; D000328:Adult; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008168:Lung / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D012129:Respiratory Function Tests; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology*; D014481:United States / Q000453:epidemiology
D000217:Acyltransferases; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1; C043403:fatty acyl ethyl ester synthase