Traffic, asthma and genetics: Combining international birth cohort data to examine genetics as a mediator of traffic-related air pollution's impact on childhood asthma.

Associations between traffic-related air pollution and incident childhood asthma can be strengthened by analysis of gene-environment interactions, but studies have typically been limited by lack of study power. We combined data from six birth cohorts on: asthma, eczema and allergic rhinitis to 7/8 years, and candidate genes. Individual-level assessment of traffic-related air pollution exposure was estimated using land use regression or dispersion modeling. A total of 11,760 children were included in the Traffic, Asthma and Genetics (TAG) Study; 6.3 % reported physician-diagnosed asthma at school-age, 16.0 % had asthma at anytime during childhood, 14.1 % had allergic rhinitis at school-age, 10.0 % had eczema at school-age and 33.1 % were sensitized to any allergen. For GSTP1 rs1138272, the prevalence of heterozygosity was 16 % (range amongst individual cohorts, 11-17 %) and homozygosity for the minor allele was 1 % (0-2 %). For GSTP1 rs1695, the prevalence of heterozygosity was 45 % (40-48 %) and homozygosity for the minor allele, 12 % (10-12 %). For TNF rs1800629, the prevalence of heterozygosity was 29 % (25-32 %) and homozygosity for the minor allele, 3 % (1-3 %). TAG comprises a rich database, the largest of its kind, for investigating the effect of genotype on the association between air pollution and childhood allergic disease

<em>GSTP1</em> and <em>TNF</em> gene variants and associations between air pollution and incident childhood asthma: The Traffic, Asthma and Genetics (TAG) study.

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&#39;s birth address using land-use regression, atmospheric modeling, and ambient monitoring data. Effect modification by variants in GSTP1 (rs1138272/Ala(114)Val and rs1695/IIe(105)Val) 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 &ge;1 GSTP1 rs1138272 minor allele were at increased risk of current asthma (OR=2.59; 95%CI: 1.43, 4.68 per 10 &micro;g/m(3) 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