GSTP1 and TNF Gene Variants and Associations between Air Pollution and Incident Childhood Asthma: The Traffic, Asthma and Genetics (TAG) Study
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Citation: MacIntyre EA, Brauer M, Melén E, Bauer CP, Bauer M, Berdel D, Bergström A, Brunekreef B, Chan-Yeung M, Klümper C, Fuertes E, Gehring U, Gref A, Heinrich J, Herbarth O, Kerkhof M, Koppelman GH, Kozyrskyj AL, Pershagen G, Postma DS, Thiering E, Tiesler CM, Carlsten C, TAG Study Group. GSTP1 and TNF Gene Variants and Associations between Air Pollution and Incident Childhood Asthma: The Traffic, Asthma and Genetics (TAG) Study. Environ Health Perspect; http://dx.doi.org/10.1289/ehp.1307459.
Received: 2 August 2013
Accepted: 24 January 2014
Advance Publication: 24 January 2014
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Background: Genetics may partially explain observed heterogeneity in associations between traffic-related air pollution and incident asthma.
Objective: To investigate the impact of gene variants associated with oxidative stress and inflammation on associations between air pollution and incident childhood asthma.
Methods: Traffic-related air pollution, asthma, wheeze, gene variant, and potential confounder data were pooled across six birth cohorts. Parents reported physician-diagnosed asthma and wheeze from birth to age 7-8 years (confirmed by pediatric allergist in two cohorts). Individual estimates of annual average air pollution (NO2, PM2.5, PM2.5 absorbance, ozone) were assigned to each child’s birth address using land-use regression, atmospheric modeling, and ambient monitoring data. Effect modification by variants in GSTP1 (rs1138272/Ala114Val and rs1695/IIe105Val) and TNF (rs1800629/G-308A) was investigated.
Results: Data on asthma, wheeze, potential confounders, at least one SNP of interest and NO2 were available for 5,115 children. GSTP1 rs1138272 and TNF rs1800629 SNPs were associated with asthma and wheeze, respectively. In relation to air pollution exposure, children with ≥1 GSTP1 rs1138272 minor allele were at increased risk of current asthma (OR=2.59; 95%CI: 1.43, 4.68 per 10µg/m3 NO2) and ever asthma (OR=1.64; 95% CI: 1.06, 2.53) compared with homozygous major allele carriers (OR=0.95; 95% CI: 0.68, 1.32 for current and OR=1.20; 95% CI: 0.98, 1.48 for ever asthma, (Bonferroni-corrected interaction p-values 0.04 and 0.01, respectively). Similarly, for GSTP1 rs1695, associations between NO2 and current and ever asthma were OR=1.43 (95% CI: 1.03, 1.98) and 1.36 (95% CI: 1.08, 1.70) respectively, for minor allele carriers compared to OR=0.82 (95%CI: 0.52, 1.32) and 1.12 (95%CI: 0.84, 1.49) for homozygous major allele carriers (Bonferroni-corrected interaction p-values 0.48 and 0.09). There were no clear differences by TNF genotype.
Conclusions: Children carrying GSTP1 rs1138272 or rs1695 minor alleles may constitute a susceptible population at increased risk of asthma associated with air pollution.
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