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Fuertes, E. ; Brauer, M.* ; MacIntyre, E.A. ; Bauer, M.* ; Bellander, T.* ; von Berg, A.* ; Berdel, D.* ; Brunekreef, B.* ; Chan-Yeung, M.* ; Gehring, U.* ; Herbarth, O.* ; Hoffmann, B.* ; Kerkhof, M.* ; Klümper, C.* ; Koletzko, S.* ; Kozyrskyj, A.* ; Kull, I.* ; Heinrich, J. ; Melén, E.* ; Pershagen, G.* ; Postma, D.* ; Tiesler, C.M. ; Carlsten, C.* ; TAG Consortium (*)

Childhood allergic rhinitis, traffic-related air pollution, and variability in the GSTP1, TNF, TLR2, and TLR4 genes: Results from the TAG study.

J. Allergy Clin. Immunol. 132, 342-352 (2013)

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BACKGROUND: Associations between traffic-related air pollution (TRAP) and allergic rhinitis remain inconsistent, possibly because of unexplored gene-environment interactions. OBJECTIVE: In a pooled analysis of 6 birth cohorts (Ntotal = 15,299), we examined whether TRAP and genetic polymorphisms related to inflammation and oxidative stress predict allergic rhinitis and sensitization. METHODS: Allergic rhinitis was defined with a doctor diagnosis or reported symptoms at age 7 or 8 years. Associations between nitrogen dioxide, particulate matter 2.5 (PM2.5) mass, PM2.5 absorbance, and ozone, estimated for each child at the year of birth, and single nucleotide polymorphisms within the GSTP1, TNF, TLR2, or TLR4 genes with allergic rhinitis and aeroallergen sensitization were examined with logistic regression. Models were stratified by genotype and interaction terms tested for gene-environment associations. RESULTS: Point estimates for associations between nitrogen dioxide, PM2.5 mass, and PM2.5 absorbance with allergic rhinitis were elevated, but only that for PM2.5 mass was statistically significant (1.37 [1.01, 1.86] per 5 μg/m(3)). This result was not robust to single-cohort exclusions. Carriers of at least 1 minor rs1800629 (TNF) or rs1927911 (TLR4) allele were consistently at an increased risk of developing allergic rhinitis (1.19 [1.00, 1.41] and 1.24 [1.01, 1.53], respectively), regardless of TRAP exposure. No evidence of gene-environment interactions was observed. CONCLUSION: The generally null effect of TRAP on allergic rhinitis and aeroallergen sensitization was not modified by the studied variants in the GSTP1, TNF, TLR2, or TLR4 genes. Children carrying a minor rs1800629 (TNF) or rs1927911 (TLR4) allele may be at a higher risk of allergic rhinitis.

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