title: Traffic-related air pollution, oxidative stress genes, and asthma (ECHRS).
abstract: 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.
authors.affiliation: Centre for Research in Environmental Epidemiology, Barcelona, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Castro-Giner
authors.forename: Nino
authors.initials: N
authors.lastname: Künzli
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Jacquemin
authors.forename: Bertil
authors.initials: B
authors.lastname: Forsberg
authors.forename: Rafael
authors.initials: R
authors.lastname: de Cid
authors.forename: Jordi
authors.initials: J
authors.lastname: Sunyer
authors.forename: Deborah
authors.initials: D
authors.lastname: Jarvis
authors.forename: David
authors.initials: D
authors.lastname: Briggs
authors.forename: Danielle
authors.initials: D
authors.lastname: Vienneau
authors.forename: Dan
authors.initials: D
authors.lastname: Norback
authors.forename: Juan R
authors.initials: JR
authors.lastname: González
authors.forename: Stefano
authors.initials: S
authors.lastname: Guerra
authors.forename: Christer
authors.initials: C
authors.lastname: Janson
authors.forename: Josep-Maria
authors.initials: JM
authors.lastname: Antó
authors.forename: Matthias
authors.initials: M
authors.lastname: Wjst
authors.forename: Joachim
authors.initials: J
authors.lastname: Heinrich
authors.forename: Xavier
authors.initials: X
authors.lastname: Estivill
authors.forename: Manolis
authors.initials: M
authors.lastname: Kogevinas
mesh_terms: 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
chemical_list: 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