Ozone exposure, antioxidant genes, and lung function in an elderly cohort: VA Normative Aging Study

Stacey E. Alexeeff ^1*, Augusto A. Litonjua ², Robert O. Wright ², Andrea Baccarelli ¹, Helen Suh ¹, David Sparrow ³, Pantel S. Vokonas ³ and Joel Schwartz ¹

¹ Harvard School of Public Health, United States
² Harvard Medical School, United States
³ Boston University School of Medicine, United States

^* To whom correspondence should be addressed. E-mail: staceyac{at}stat.cmu.edu.

Accepted 4 April 2008

Abstract

Background: Ozone exposure is known to cause oxidative stress. We investigated the acute effects of ozone (O3) on lung function in the elderly, a suspected risk group. We then investigated whether genetic polymorphisms of antioxidant genes (heme oxygenase-1 [HMOX1] and glutathione S-transferase pi [GSTP1]) modified these associations.

Methods: We studied 1,100 elderly men from the Normative Aging Study whose lung function (forced vital capacity [FVC] and forced expiratory volume in one second [FEV1]) was measured every 3 years from 1995-2005. We genotyped the GSTP1 Ile105Val and Ala114Val polymorphisms and the (GT)n repeat polymorphism in the HMOX1 promoter, classifying repeats as short (n<25) or long (n25). Ambient O3 was measured continuously at locations in the Greater Boston area. We used mixed linear models, adjusting for known confounders.

Results: A 15 ppb increase in O3 during the previous 48 hours was associated with a 1.25% decrease in FEV1 (95% CI: -1.96%, -0.54%). This estimated effect was worsened with either the presence of a long (GT)n repeat in HMOX1 (-1.38%, 95% CI: -2.11%, -0.65) or the presence of an allele coding for Val105 in GSTP1 (-1.69%, 95% CI: -2.63%, -0.75). A stronger estimated effect of O3 on FEV1 was found in subjects carrying both the GSTP1 105Val variant and the HMOX1 long (GT)n repeat (-1.94%, 95% CI: -2.89%, -0.98%). Similar associations were also found between FVC and ozone exposure.

Conclusions: Our results suggest that ozone has an acute effect on lung function in the elderly, and the effects may be modified by the presence of specific polymorphisms in antioxidant genes.