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Asthma
Toll-like receptor 2 and 4 genes influence susceptibility to adverse effects of traffic-related air pollution on childhood asthma
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  1. M Kerkhof1,
  2. D S Postma2,
  3. B Brunekreef3,4,
  4. N E Reijmerink2,5,
  5. A H Wijga6,
  6. J C de Jongste7,
  7. U Gehring3,
  8. G H Koppelman8
  1. 1Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  2. 2Department of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  3. 3Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands
  4. 4Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands
  5. 5Department of Pediatrics, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  6. 6Center for Prevention and Health Services Research, National Institute for Public Health and Environment, Bilthoven, The Netherlands
  7. 7Department of Pediatrics/Respiratory Medicine, Erasmus University, Rotterdam, The Netherlands
  8. 8Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  1. Correspondence to Dr M Kerkhof, Department of Epidemiology, University Medical Center Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands; m.kerkhof{at}epi.umcg.nl

Abstract

Background Epidemiological studies have reported adverse effects of ambient air pollution on the prevalence of asthma. Laboratory studies have suggested that innate immune responses are involved.

Objective A study was undertaken to determine whether the Toll-like receptor 2 and 4 genes (TLR2 and TLR4) influence the susceptibility to adverse effects of traffic-related air pollution with respect to the prevalence of childhood asthma.

Methods Haplotype tagging single nucleotide polymorphisms (SNPs) in the TLR2 (n=4) and TLR4 genes (n=9) were genotyped in 916 children from the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort. Exposure to particulate matter (PM2.5), soot and nitrogen dioxide (NO2) at the birth address was estimated by land use regression models. Interactions between levels of pollutants and SNPs in relation to annual questionnaire reports of asthma diagnosis and symptoms from birth up to 8 years of age were analysed longitudinally by generalised estimating equations.

Results Two TLR2 SNPs and four TLR4 SNPs significantly modified the effect of air pollution on the prevalence of doctor-diagnosed asthma from birth up to 8 years of age. The risk of having doctor-diagnosed asthma increased with increasing PM2.5 levels in children with at least one copy of the TLR2 rs4696480 A allele (OR 2.0 (95% CI 1.2 to 3.1) for an interquartile range increase in exposure). Similar observations were present with the following TLR4 genotypes: rs2770150 TC (OR 2.0 (95% CI 1.1 to 3.6)), rs10759931 GG (OR 2.6 (95% CI 1.4 to 4.9)), rs6478317 GG (OR 2.2 (95% CI 1.2 to 4.3)), rs10759932 CT or CC (OR 2.9 (95% CI 1.2 to 6.9)) and rs1927911 TT (OR 4.4 (95% CI 1.7 to 11.7)).

Conclusions Variant alleles of TLR2 and TLR4 genes influence the susceptibility to adverse effects of traffic-related air pollution on childhood asthma.

  • Asthma
  • air pollution
  • genetics
  • Toll-Like Receptors
  • interaction
  • asthma epidemiology, asthma genetics
  • paediatric asthma

https://doi.org/10.1136/thx.2009.119636

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    Footnotes

    • Funding The Prevention and Incidence of Asthma and Mite Allergy (PIAMA) study is funded by the Netherlands Organisation for Health Research and Development, the Netherlands Asthma Foundation, the Netherlands Ministry of Planning, Housing and the Environment, the Netherlands Ministry of Health, Welfare and Sport and the National Institute for Public Health and the Environment.

    • Competing interests None.

    • Ethics approval The study protocol was approved by the medical ethics committees of the participating institutions.

    • Provenance and peer review Not commissioned; externally peer reviewed.