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

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 NO2 estimates were available. Home addresses were geocoded and linked to modeled outdoor NO2 estimates, as a market 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 NO2 and asthma prevalence was significant for carriers of the most common genotypes of NQ01 rs2917666 [odds ratio (OR) = 1.54; 95% confidence interval (Cl), 1.10-2.24], TNFA rs2844484 (OR = 2.02; 95% CI, 1.30-3.27). For new-onset asthma, the effect of NO2 was significant for the most common genotype of NQ01 rs2917666 (OR = 1.52; 95%) Cl, 1.09-2.16). A significant interaction was found between NQ01 rs2917666 and NO2 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.