title: Childhood allergic rhinitis, traffic-related air pollution, and variability in the GSTP1, TNF, TLR2, and TLR4 genes: results from the TAG Study.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.
authors: Elaine
authors: E
authors: Fuertes
authors: Michael
authors: M
authors: Brauer
authors: Elaina
authors: E
authors: MacIntyre
authors: Mario
authors: M
authors: Bauer
authors: Tom
authors: T
authors: Bellander
authors: Andrea
authors: A
authors: von Berg
authors: Dietrich
authors: D
authors: Berdel
authors: Bert
authors: B
authors: Brunekreef
authors: Moira
authors: M
authors: Chan-Yeung
authors: Ulrike
authors: U
authors: Gehring
authors: Olf
authors: O
authors: Herbarth
authors: Barbara
authors: B
authors: Hoffmann
authors: Marjan
authors: M
authors: Kerkhof
authors: Claudia
authors: C
authors: Klümper
authors: Sibylle
authors: S
authors: Koletzko
authors: Anita
authors: A
authors: Kozyrskyj
authors: Inger
authors: I
authors: Kull
authors: Joachim
authors: J
authors: Heinrich
authors: Erik
authors: E
authors: Melén
authors: Göran
authors: G
authors: Pershagen
authors: Dirkje
authors: D
authors: Postma
authors: Carla M T
authors: CM
authors: Tiesler
authors: Chris
authors: C
authors: Carlsten
mesh_terms: D000393:Air Pollutants / Q000009:adverse effects / Q000032:analysis; D000397:Air Pollution / Q000009:adverse effects* / Q000032:analysis; D002648:Child; D015331:Cohort Studies; D005260:Female; D059647:Gene-Environment Interaction; D051549:Glutathione S-Transferase pi / Q000235:genetics; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D065631:Rhinitis, Allergic; D012221:Rhinitis, Allergic, Perennial / Q000209:etiology / Q000235:genetics*; D051195:Toll-Like Receptor 2 / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D001335:Vehicle Emissions; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi
keywords: APMoSPHERE; Air Pollution Modelling for Support to Policy on Health and Environmental Risk in Europe; BAMSE; CAPPS; Canadian Asthma Primary Prevention Study; Childhood allergic rhinitis; Children, Allergy, Milieu, Stockholm, Epidemiological Survey; GINIplus; GSTP1; German Infant study on the influence of Nutritional Intervention plus environmental and genetic influences on allergy development; Glutathione-S-transferase pi 1; LISAplus; LUR; Land-use regression; Lifestyle related factors, Immune System and the development of Allergies in Childhood plus the influence of traffic emissions and genetics study; NO(2); Nitrogen dioxide; OR; Odds ratio; PIAMA; PM; Particulate matter; Prevention and Incidence of Asthma and Mite Allergy; SAGE; SNP; Single nucleotide polymorphism; Study of Asthma, Genes, and Environment; TAG; TLR; TLR4; TNF; TRAP; Toll-like receptor; Traffic, Asthma, and Genetics; Traffic-related air pollution; air pollution; genetics; interaction