Traffic-Related Air Pollution, Oxidative Stress Genes, and Asthma (ECHRS)

Centre for Research in Environmental Epidemiology, Barcelona, Spain.
Environmental Health Perspectives (Impact Factor: 7.98). 12/2009; 117(12):1919-24. DOI: 10.1289/ehp.0900589
Source: PubMed


Traffic-related air pollution is related with asthma, and this association may be modified by genetic factors.
We investigated the role of genetic polymorphisms potentially modifying the association between home outdoor levels of modeled nitrogen dioxide and asthma.
Adults from 13 cities of the second European Community Respiratory Health Survey (ECRHS II) were included (n = 2,920), for whom both DNA and outdoor NO(2) estimates were available. Home addresses were geocoded and linked to modeled outdoor NO(2) estimates, as a marker of local traffic-related pollution. We examined asthma prevalence and evaluated polymorphisms in genes involved in oxidative stress pathways [gluthatione S-transferases M1 (GSTM1), T1 (GSTT1), and P1 (GSTP1) and NAD(P)H:quinine oxidoreductase (NQO1)], inflammatory response [tumor necrosis factor alpha (TNFA)], immunologic response [Toll-like receptor 4 (TLR4)], and airway reactivity [adrenergic receptor beta2 (ADRB2)].
The association between modeled NO(2) and asthma prevalence was significant for carriers of the most common genotypes of NQO1 rs2917666 [odds ratio (OR) = 1.54; 95% confidence interval (CI), 1.10-2.24], TNFA rs2844484 (OR = 2.02; 95% CI, 1.30-3.27). For new-onset asthma, the effect of NO(2) was significant for the most common genotype of NQO1 rs2917666 (OR = 1.52; 95% CI, 1.09-2.16). A significant interaction was found between NQO1 rs2917666 and NO(2) for asthma prevalence (p = 0.02) and new-onset asthma (p = 0.04).
Genetic polymorphisms in the NQO1 gene are related to asthma susceptibility among persons exposed to local traffic-related air pollution. This points to the importance of antioxidant pathways in the protection against the effects of air pollution on asthma.

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    • "Following this approach in our previous study [19], we pointed out the potential relevance of toxicogenomic mechanisms of BA in the modern world and proposed that genes for xenobiotic-metabolizing enzymes would be the most appropriate candidate genes for asthma susceptibility whose effects on the disease risk can be associated with exposure to air pollution. Due to the fact that air pollutants are the sources of reactive oxygen species (ROS), genes involved in oxidative stress can potentiate harmful effects of xenobiotics on the respiratory system [20] [21]. It is well known that oxidative stress resulting from an increased amount of ROS and an imbalance between oxidants and antioxidants plays a role in the molecular mechanisms underlying BA [22] [23] [24]. "
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    • "In agreement with the current study results, no association of the disease with GSTM1 null genotype was noted by several studies in different populations [2,12-16,18]. However, an increased risk was seen in individuals with this genotype in some reports [3,17,19-24]. "
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    • "For NQO1, association has been described between the " slow " genotype and asthma [30]. Other studies described associations in combination with the homozygous deletion of GSTM1 [31] or with local traffic-related air pollution [32]. These findings point out to the importance of antioxidant pathways in the protection against the effects of air pollution for asthma. "
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    ABSTRACT: Objective: Obstructive respiratory diseases, mainly the chronic obstructive pulmonary disease (COPD) and asthma, are associated with functional polymorphisms of xenobiotic-metabolizing enzymes (XMEs). To date, association for obstructive bronchitis has not been described. Material/methods: In this study, we investigated the genotypes from 26 functional polymorphisms of 20 XMEs in children (n, 1028) at the age of 6 years from the German prospective birth cohort study (LISAplus) and analyzed the associations between genotypes and obstructive bronchitis. Results: For the first time, we found noteworthy gene-disease associations for the functional PON1 M55L and EPHX1 H139R polymorphisms and gene-environment associations for the functional COMT V158M and NQO1 P187S polymorphisms after stratification for maternal active smoking behaviour during pregnancy. The noteworthy associations were substantiated by the biological findings that all the risk genotypes belong to genes involved in oxidative stress and code for proteins with a fast enzymatic activity or concomitantly appear in common estrogene-metabolizing pathway (COMT, NQO1). Conclusion: The oxidative stress has to be taken into account in mechanism of the obstructive bronchitis in early childhood. The risk genotypes may serve as risk factors for respiratory obstruction rather than for signs of COPD or asthma.
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