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

• Published in: Journal of allergy and clinical immunology Vol. 132; no. 2; pp. 342 - 352.e2
• Main Authors: Fuertes, Elaine, MSc, Brauer, Michael, PhD, MacIntyre, Elaina, PhD, Bauer, Mario, MD, Bellander, Tom, MD, von Berg, Andrea, MD, PhD, Berdel, Dietrich, MD, PhD, Brunekreef, Bert, PhD, Chan-Yeung, Moira, MB, Gehring, Ulrike, PhD, Herbarth, Olf, PhD, Hoffmann, Barbara, MD, MPH, Kerkhof, Marjan, PhD, Klümper, Claudia, DrPH, Koletzko, Sibylle, MD, PhD, Kozyrskyj, Anita, PhD, Kull, Inger, PhD, Heinrich, Joachim, PhD, Melén, Erik, MD, PhD, Pershagen, Göran, MD, PhD, Postma, Dirkje, PhD, Tiesler, Carla M.T., MSc, Carlsten, Chris, MD, MPH
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.08.2013; Elsevier
• Subjects: Air Pollutants - adverse effects; Air Pollutants - analysis; air pollution; Air Pollution - adverse effects; Air Pollution - analysis; Allergy and Immunology; Biological and medical sciences; Child; Childhood allergic rhinitis; Cohort Studies; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene-Environment Interaction; genetics; Glutathione S-Transferase pi - genetics; Humans; interaction; Male; Medical sciences; Medicin och hälsovetenskap; Polymorphism, Single Nucleotide; Rhinitis, Allergic; Rhinitis, Allergic, Perennial - etiology; Rhinitis, Allergic, Perennial - genetics; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; TLR4; TNF; Toll-Like Receptor 2 - genetics; Toll-Like Receptor 4 - genetics; Tumor Necrosis Factor-alpha - genetics; Vehicle Emissions - toxicity; BAMSE; Traffic-related air pollution; GSTP1; German Infant study on the influence of Nutritional Intervention plus environmental and genetic influences on allergy development; Childhood allergic rhinitis; SAGE; TRAP; TNF; Lifestyle related factors, Immune System and the development of Allergies in Childhood plus the influence of traffic emissions and genetics study; LISAplus; genetics; Air Pollution Modelling for Support to Policy on Health and Environmental Risk in Europe; SNP; GINIplus; TLR; Prevention and Incidence of Asthma and Mite Allergy; Toll-like receptor; OR; LUR; Children, Allergy, Milieu, Stockholm, Epidemiological Survey; PIAMA; Particulate matter; NO 2; interaction; Odds ratio; air pollution; Study of Asthma, Genes, and Environment; Traffic, Asthma, and Genetics; CAPPS; Single nucleotide polymorphism; TAG; Glutathione- S-transferase pi 1; Nitrogen dioxide; TLR4; Canadian Asthma Primary Prevention Study; PM; Land-use regression; APMoSPHERE; NO2; Human; Allergy; Immunopathology; Nose disease; Toll like receptor 4; Rhinitis; Enzyme; Isozyme; Toll like receptor 2; Transferases; Variability; Cytokine; Immunology; Gene; Tumor necrosis factor; Glutathione transferase; ENT disease; Genetics; Air pollution; Child; NO; Glutathione-S-transferase pi 1
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2013.03.007

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/m3 ). 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.