Traffic-related air pollution, oxidative stress genes, and asthma (ECHRS).
BACKGROUND
Traffic-related air pollution is related with asthma, and this association may be modified by genetic factors.


OBJECTIVE
We investigated the role of genetic polymorphisms potentially modifying the association between home outdoor levels of modeled nitrogen dioxide and asthma.


METHODS
Adults from 13 cities of the second European Community Respiratory Health Survey (ECRHS II) were included (n = 2,920), for whom both DNA and outdoor NO(2) estimates were available. Home addresses were geocoded and linked to modeled outdoor NO(2) estimates, as a marker of local traffic-related pollution. We examined asthma prevalence and evaluated polymorphisms in genes involved in oxidative stress pathways [gluthatione S-transferases M1 (GSTM1), T1 (GSTT1), and P1 (GSTP1) and NAD(P)H:quinine oxidoreductase (NQO1)], inflammatory response [tumor necrosis factor alpha (TNFA)], immunologic response [Toll-like receptor 4 (TLR4)], and airway reactivity [adrenergic receptor beta2 (ADRB2)].


RESULTS
The association between modeled NO(2) and asthma prevalence was significant for carriers of the most common genotypes of NQO1 rs2917666 [odds ratio (OR) = 1.54; 95% confidence interval (CI), 1.10-2.24], TNFA rs2844484 (OR = 2.02; 95% CI, 1.30-3.27). For new-onset asthma, the effect of NO(2) was significant for the most common genotype of NQO1 rs2917666 (OR = 1.52; 95% CI, 1.09-2.16). A significant interaction was found between NQO1 rs2917666 and NO(2) for asthma prevalence (p = 0.02) and new-onset asthma (p = 0.04).


CONCLUSIONS
Genetic polymorphisms in the NQO1 gene are related to asthma susceptibility among persons exposed to local traffic-related air pollution. This points to the importance of antioxidant pathways in the protection against the effects of air pollution on asthma.
Castro-Giner
Francesc
F
Centre for Research in Environmental Epidemiology, Barcelona, Spain.
Künzli
Nino
N
Jacquemin
Bénédicte
B
Forsberg
Bertil
B
de Cid
Rafael
R
Sunyer
Jordi
J
Jarvis
Deborah
D
Briggs
David
D
Vienneau
Danielle
D
Norback
Dan
D
González
Juan R
JR
Guerra
Stefano
S
Janson
Christer
C
Antó
Josep-Maria
JM
Wjst
Matthias
M
Heinrich
Joachim
J
Estivill
Xavier
X
Kogevinas
Manolis
M
D000328:Adult; D000397:Air Pollution / Q000009:adverse effects*; D001249:Asthma / Q000453:epidemiology / Q000209:etiology*; D005260:Female; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D018986:Motor Vehicles; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D009569:Nitric Oxide / Q000032:analysis; D018384:Oxidative Stress; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence
D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D016660:NAD(P)H Dehydrogenase (Quinone); D009569:Nitric Oxide; C447479:NQO1 protein, human; C496556:GSTP1 protein, human