Glutathione S-transferase variants and their interaction with smoking on lung function

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

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62 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)388-394
Number of pages7
JournalAmerican journal of respiratory and critical care medicine
Volume170
Issue number4
DOIs
StatePublished - Aug 15 2004

Keywords

  • Cigarette smoking
  • FEV
  • Gene-environment interaction
  • Genetic polymorphism
  • Glutathione S-transferase

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