Traffic-Related Air Pollution, Oxidative Stress Genes, and Asthma (ECHRS)
Castro-Giner, Francesc, Kunzli, Nino, Jacquemin, Benedicte, Forsberg, Bertil, Cid, Rafael de, Sunyer, Jordi, Janvis, Deborah, Briggs, David, Vienneau, Danielle, Norback, Dan, Gonzalez, Juan R., Guerra, Stefano, Janson, Christer, Anto, Josep-Maria, Wjst, Matthias, Heinrich, Joachim, Estivill, Xavier, Kogevinas, Manolis, Environmental Health Perspectives
BACKGROUND: Traffic-related air pollution is related with asthma, and this association may be modified by genetic factors.
OBJECTIVES: We investigated the role of genetic polymorphisms potentially modifying the association between home outdoor levels of modeled nitrogen dioxide and asthma.
METHODS: 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.sub.2] estimates were available. Home addresses were geocoded and linked to modeled outdoor [NO.sub.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 [beta]2 (ADRB2)].
RESULTS: The association between modeled [NO.sub.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.sub.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.sub.2] for asthma prevalence (p = 0.02) and new-onset asthma (p = 0.04).
CONCLUSIONS: 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.
KEY WORDS: air pollution, asthma, gene polymorphisms, genetics, nitrogen dioxide, oxidative stress, traffic pollution. Environ Health Perspect 117:1919-1924 (2009). doi:10.1289/ehp.0900589 available via http://dx.doi.org/ [Online 23 July 2009]
Asthma is a complex disease with both genetic and environmental components. The interaction between genetic predisposition and environmental factors is likely to have an important role in the etiology and prognosis of the disease. However, only few studies have addressed gene--environment interactions in asthma (Castro-Giner et al. 2006; London 2007; Yang et al. 2008).
Air pollution contributes to the development of asthma (Brauer et al. 2007; Gehring et al. 2002; Jacquemin et al. 2009; McConnell et al. 2006; Modig et al. 2006) and asthma exacerbations (D'Amato et al. 2005; Heinrich and Wichmann 2004; Kunzli et al. 2000; Nel 2005). Traffic-related pollutants such as particulate matter, nitrogen dioxide, and ozone are strong oxidants (D'Amato et al. 2005), leading to the production of reactive oxygen species (ROS). Oxidative stress triggers the inflammatory response and cytokine production (Kelly 2003; Nel 2005). It is plausible that genetic variants involved in inflammation and protection against ROS may influence the response to air pollutants. Polymorphisms in oxidative stress genes NAD(P)H:quinine oxidoreductase [NQO1, GeneID 1728 (Entrez Gene 2008)] and gluthatione S-transferases M1 [GSTM1, GeneID 2944 (Entrez Gene 2008)] and P1 [GSTP1, GeneID 2950 (Entrez Gene 2008)] have been associated with a decrease on pulmonary function (Bergamaschi et al. 2001; Romieu et al. 2004; Yang et al. 2005) and with increased allergic response (Gilliland et al. 2004, 2006), respiratory symptoms, and asthma (David et al. 2003; Lee et al. 2004; Li et al. 2006; Romieu et al. 2006) in response to air pollutants, including [O.sub.3] and diesel exhaust particles (DEP). Variants in the proinflammatory cytokine gene tumor necrosis factor (X [TNFA, GeneID 7124 (Entrez Gene 2008)] have been linked to decrease in pulmonary function (Winterton et al. …