GSTP1 and TNF 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
Our aim was 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 7-8 years of age (confirmed by pediatric allergist in two cohorts). Individual estimates of annual average air pollution [nitrogen dioxide (NO2), particulate matter ≤ 2.5 μm (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 one or more GSTP1 rs1138272 minor allele were at increased risk of current asthma [odds ratio (OR) = 2.59; 95% CI: 1.43, 4.68 per 10 μg/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 = 0.04 and 0.01, respectively). Similarly, for GSTP1 rs1695, associations between NO2 and current and ever asthma had ORs of 1.43 (95% CI: 1.03, 1.98) and 1.36 (95% CI: 1.08, 1.70), respectively, for minor allele carriers compared with ORs of 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.
School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.
Elaina A
EA
MacIntyre
Michael
M
Brauer
Erik
E
Melén
Carl Peter
CP
Bauer
Mario
M
Bauer
Dietrich
D
Berdel
Anna
A
Bergström
Bert
B
Brunekreef
Moira
M
Chan-Yeung
Claudia
C
Klümper
Elaine
E
Fuertes
Ulrike
U
Gehring
Anna
A
Gref
Joachim
J
Heinrich
Olf
O
Herbarth
Marjan
M
Kerkhof
Gerard H
GH
Koppelman
Anita L
AL
Kozyrskyj
Göran
G
Pershagen
Dirkje S
DS
Postma
Elisabeth
E
Thiering
Carla M T
CM
Tiesler
Christopher
C
Carlsten
D000393:Air Pollutants / Q000633:toxicity*; D000397:Air Pollution / Q000009:adverse effects*; D001249:Asthma / Q000139:chemically induced* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D052638:Particulate Matter / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D001335:Vehicle Emissions / Q000633:toxicity
D000393:Air Pollutants; D052638:Particulate Matter; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D001335:Vehicle Emissions; D051549:Glutathione S-Transferase pi