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Effects of antioxidant enzyme polymorphisms on ozone-induced lung function changes.

ABSTRACT: Chronic exposure to ozone (O(3)) can cause changes in lung function that may reflect remodelling of small airways. It is likely that antioxidant enzyme function affects susceptibility to O(3). The aim of the present study was to determine whether polymorphisms in antioxidant enzyme (GSTM1, GSTP1 and NQO1) genes affect the risk of lung function changes related to chronic exposure to O(3). In total, 210 young adults who participated in a previous study, which showed a relationship between lifetime exposure to O(3) and decreased lung function, were genotyped. Multivariable linear regression was used to model sex-specific associations between genotypes and O(3)-related lung function changes, adjusting for height, weight, lifetime exposure to nitrogen dioxide and particles with a 50% cut-off aerodynamic diameter of 10 mum, and self-identified race/ethnicity. The GSTM1-null/NQO1 Pro187Pro-combination genotype was significantly associated with increased risk of an O(3)-related decrease in mean forced expiratory flow between 25-75% of forced vital capacity in females (parameter estimate+/-se -75+/-35 mL.s(-1)), while the GSTP1 Val105 variant genotypes were significantly associated with greater risk of an O(3)-related decrease in mean forced expiratory flow at 75% of forced vital capacity in males (-81+/-31 mL.s(-1)). GSTM1-null status was not significantly associated with any O(3)-related changes in lung function in either sex. The current authors conclude that the effects of antioxidant enzyme gene polymorphisms on the risk of decreased lung function related to chronic exposure to ozone may be modified by sex-specific factors.

SUBMITTER: Chen C

PROVIDER: S-EPMC3282174 | biostudies-literature | 2007 Oct

REPOSITORIES: biostudies-literature

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Effects of antioxidant enzyme polymorphisms on ozone-induced lung function changes.

Chen C C Arjomandi M M Tager I B IB Holland N N Balmes J R JR

The European respiratory journal 20070725 4

Chronic exposure to ozone (O(3)) can cause changes in lung function that may reflect remodelling of small airways. It is likely that antioxidant enzyme function affects susceptibility to O(3). The aim of the present study was to determine whether polymorphisms in antioxidant enzyme (GSTM1, GSTP1 and NQO1) genes affect the risk of lung function changes related to chronic exposure to O(3). In total, 210 young adults who participated in a previous study, which showed a relationship between lifetime ...[more]

PMID: 17652311

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Project description:The potential effects of combinations of dilute whole diesel exhaust (DE) and ozone (O?), each a common component of ambient airborne pollutant mixtures, on lung function were examined. Healthy young human volunteers were exposed for 2 hr to pollutants while exercising (~50 L/min) intermittently on two consecutive days. Day 1 exposures were either to filtered air, DE (300 ?g/m³), O? (0.300 ppm), or the combination of both pollutants. On Day 2 all exposures were to O? (0.300 ppm), and Day 3 served as a followup observation day. Lung function was assessed by spirometry just prior to, immediately after, and up to 4 hr post-exposure on each exposure day. Functional pulmonary responses to the pollutants were also characterized based on stratification by glutathione S-transferase mu 1 (GSTM1) genotype. On Day 1, exposure to air or DE did not change FEV1 or FVC in the subject population (n?=?15). The co-exposure to O? and DE decreased FEV1 (17.6%) to a greater extent than O? alone (9.9%). To test for synergistic exposure effects, i.e., in a greater than additive fashion, FEV1 changes post individual O? and DE exposures were summed together and compared to the combined DE and O? exposure; the p value was 0.057. On Day 2, subjects who received DE exposure on Day 1 had a larger FEV1 decrement (14.7%) immediately after the O? exposure than the individuals' matched response following a Day 1 air exposure (10.9%). GSTM1 genotype did not affect the magnitude of lung function changes in a significant fashion. These data suggest that altered respiratory responses to the combination of O? and DE exposure can be observed showing a greater than additive manner. In addition, O?-induced lung function decrements are greater with a prior exposure to DE compared to a prior exposure to filtered air. Based on the joint occurrence of these pollutants in the ambient environment, the potential exists for interactions in more than an additive fashion affecting lung physiological processes.

Dataset Information

Effects of antioxidant enzyme polymorphisms on ozone-induced lung function changes.

Publications

Effects of antioxidant enzyme polymorphisms on ozone-induced lung function changes.

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