Anke Hüls1, Claudia Klümper1,2, Elaina A MacIntyre3,4, Michael Brauer5, Erik Melén6,7,8, Mario Bauer9, Dietrich Berdel10, Anna Bergström6,7, Bert Brunekreef11,12, Moira Chan-Yeung13, Elaine Fuertes14,15,16, Ulrike Gehring11, Anna Gref6, Joachim Heinrich17,18, Marie Standl17, Irina Lehmann9, Marjan Kerkhof19,20, Gerard H Koppelman21,22, Anita L Kozyrskyj23,24, Göran Pershagen6,7, Christopher Carlsten5,13,25, Ursula Krämer1, Tamara Schikowski1. 1. IUF - Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany. 2. Hochschule Hamm-Lippstadt, Hamm, Germany. 3. Environmental and Occupational Health, Public Health Ontario, Toronto, ON, Canada. 4. Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada. 5. School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada. 6. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. 7. Centre for Occupational and Environmental Medicine, Stockholm County Council, Stockholm, Sweden. 8. Sachs Children's Hospital, Stockholm, Sweden. 9. Department for Environmental Immunology, Helmholtz Centre for Environmental Research-UFZ, Leipzig, Germany. 10. Department of Pediatrics, Marien-Hospital Wesel, Research Institute, Wesel, Germany. 11. Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands. 12. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. 13. Department of Medicine, University of British Columbia, Vancouver, BC, Canada. 14. ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain. 15. Universitat Pompeu Fabra (UPF), Barcelona, Spain. 16. CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain. 17. Institute of Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany. 18. Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Inner City Clinic, University Hospital of Munich (LMU), Munich, Germany. 19. Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 20. Observational and Pragmatic Research Institute, Singapore. 21. Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 22. Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 23. Department of Pediatrics, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB, Canada. 24. School of Public Health, University of Alberta, Edmonton, AB, Canada. 25. Institute for Heart and Lung Health, Vancouver, BC, Canada.
Abstract
BACKGROUND: Associations between traffic-related air pollution (TRAP) and childhood atopic dermatitis (AD) remain inconsistent, possibly due to unexplored gene-environment interactions. The aim of this study was to examine whether a potential effect of TRAP on AD prevalence in children is modified by selected single nucleotide polymorphisms (SNPs) related to oxidative stress and inflammation. METHODS: Doctor-diagnosed AD up to age 2 years and at 7-8 years, as well as AD symptoms up to age 2 years, was assessed using parental-reported questionnaires in six birth cohorts (N = 5685). Associations of nitrogen dioxide (NO2 ) estimated at the home address of each child at birth and nine SNPs within the GSTP1, TNF, TLR2, or TLR4 genes with AD were examined. Weighted genetic risk scores (GRS) were calculated from the above SNPs and used to estimate combined marginal genetic effects of oxidative stress and inflammation on AD and its interaction with TRAP. RESULTS: GRS was associated with childhood AD and modified the association between NO2 and doctor-diagnosed AD up to the age of 2 years (P(interaction) = .029). This interaction was mainly driven by a higher susceptibility to air pollution in TNF rs1800629 minor allele (A) carriers. TRAP was not associated with the prevalence of AD in the general population. CONCLUSIONS: The marginal genetic association of a weighted GRS from GSTP1, TNF, TLR2, and TLR4SNPs and its interaction with air pollution supports the role of oxidative stress and inflammation in AD.
BACKGROUND: Associations between traffic-related air pollution (TRAP) and childhood atopic dermatitis (AD) remain inconsistent, possibly due to unexplored gene-environment interactions. The aim of this study was to examine whether a potential effect of TRAP on AD prevalence in children is modified by selected single nucleotide polymorphisms (SNPs) related to oxidative stress and inflammation. METHODS: Doctor-diagnosed AD up to age 2 years and at 7-8 years, as well as AD symptoms up to age 2 years, was assessed using parental-reported questionnaires in six birth cohorts (N = 5685). Associations of nitrogen dioxide (NO2 ) estimated at the home address of each child at birth and nine SNPs within the GSTP1, TNF, TLR2, or TLR4 genes with AD were examined. Weighted genetic risk scores (GRS) were calculated from the above SNPs and used to estimate combined marginal genetic effects of oxidative stress and inflammation on AD and its interaction with TRAP. RESULTS: GRS was associated with childhood AD and modified the association between NO2 and doctor-diagnosed AD up to the age of 2 years (P(interaction) = .029). This interaction was mainly driven by a higher susceptibility to air pollution in TNFrs1800629 minor allele (A) carriers. TRAP was not associated with the prevalence of AD in the general population. CONCLUSIONS: The marginal genetic association of a weighted GRS from GSTP1, TNF, TLR2, and TLR4SNPs and its interaction with air pollution supports the role of oxidative stress and inflammation in AD.
Authors: Irini M Dijkhoff; Barbara Drasler; Bedia Begum Karakocak; Alke Petri-Fink; Giuseppe Valacchi; Marc Eeman; Barbara Rothen-Rutishauser Journal: Part Fibre Toxicol Date: 2020-07-25 Impact factor: 9.400
Authors: Jolanta Gromadzinska; Kinga Polanska; Lucyna Kozlowska; Karolina Mikolajewska; Iwona Stelmach; Joanna Jerzyńska; Włodzimierz Stelmach; Mariusz Grzesiak; Wojciech Hanke; Wojciech Wasowicz Journal: Int J Environ Res Public Health Date: 2018-06-12 Impact factor: 3.390