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Open AccessArticle

DNA Methylation in Inflammatory Pathways Modifies the Association between BMI and Adult-Onset Non-Atopic Asthma

1
Swiss Tropical and Public Health Institute, 4051 Basel, Switzerland
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Department of Public Health, University of Basel, 4001 Basel, Switzerland
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International Agency for Research on Cancer, 69372 Lyon, France
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ISGlobal, Barcelona Institute for Global Health, 08003 Barcelona, Spain
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Universitat Pompeu Fabra (UPF), 08002 Barcelona, Spain
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CIBER Epidemiología y Salud Pública (CIBERESP), 08005 Barcelona, Spain
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Department of Economics, Business and Statistics, University of Palermo, 90128 Palermo, Italy
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Environmental Epidemiology Division, Utrecht University, Institute for Risk Assessment Sciences, 3584CM Utrecht, The Netherlands
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Population Health and Occupational Disease, National Heart and Lung Institute, Imperial College, London SW3 6LR, UK
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Division of Genetic Epidemiology, Medical University of Innsbruck, 6020 Innsbruck, Austria
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MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK
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Italian Institute for Genomic Medicine (IIGM), 10126 Turin, Italy
*
Author to whom correspondence should be addressed.
Int. J. Environ. Res. Public Health 2019, 16(4), 600; https://doi.org/10.3390/ijerph16040600
Received: 20 November 2018 / Revised: 14 February 2019 / Accepted: 15 February 2019 / Published: 19 February 2019
A high body mass (BMI) index has repeatedly been associated with non-atopic asthma, but the biological mechanism linking obesity to asthma is still poorly understood. We aimed to test the hypothesis that inflammation and/or innate immunity plays a role in the obesity-asthma link. DNA methylome was measured in blood samples of 61 non-atopic participants with asthma and 146 non-atopic participants without asthma (non-smokers for at least 10 years) taking part in the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) study. Modification by DNA methylation of the association of BMI or BMI change over 10 years with adult-onset asthma was examined at each CpG site and differentially methylated region. Pathway enrichment tests were conducted for genes in a priori curated inflammatory pathways and the NLRP3-IL1B-IL17 axis. The latter was chosen on the basis of previous work in mice. Inflammatory pathways including glucocorticoid/PPAR signaling (p = 0.0023), MAPK signaling (p = 0.013), NF-κB signaling (p = 0.031), and PI3K/AKT signaling (p = 0.031) were enriched for the effect modification of BMI, while NLRP3-IL1B-IL17 axis was enriched for the effect modification of BMI change over 10 years (p = 0.046). DNA methylation measured in peripheral blood is consistent with inflammation as a link between BMI and adult-onset asthma and with the NLRP3-IL1B-IL17 axis as a link between BMI change over 10 years and adult-onset asthma in non-atopic participants. View Full-Text
Keywords: adult-onset asthma; non-atopic asthma; obesity; inflammation; innate immunity; epigenetics; DNA methylation; epigenome-wide association study adult-onset asthma; non-atopic asthma; obesity; inflammation; innate immunity; epigenetics; DNA methylation; epigenome-wide association study
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MDPI and ACS Style

Jeong, A.; Imboden, M.; Ghantous, A.; Novoloaca, A.; Carsin, A.-E.; Kogevinas, M.; Schindler, C.; Lovison, G.; Herceg, Z.; Cuenin, C.; Vermeulen, R.; Jarvis, D.; Amaral, A.F.S.; Kronenberg, F.; Vineis, P.; Probst-Hensch, N. DNA Methylation in Inflammatory Pathways Modifies the Association between BMI and Adult-Onset Non-Atopic Asthma. Int. J. Environ. Res. Public Health 2019, 16, 600. https://doi.org/10.3390/ijerph16040600

AMA Style

Jeong A, Imboden M, Ghantous A, Novoloaca A, Carsin A-E, Kogevinas M, Schindler C, Lovison G, Herceg Z, Cuenin C, Vermeulen R, Jarvis D, Amaral AFS, Kronenberg F, Vineis P, Probst-Hensch N. DNA Methylation in Inflammatory Pathways Modifies the Association between BMI and Adult-Onset Non-Atopic Asthma. International Journal of Environmental Research and Public Health. 2019; 16(4):600. https://doi.org/10.3390/ijerph16040600

Chicago/Turabian Style

Jeong, Ayoung; Imboden, Medea; Ghantous, Akram; Novoloaca, Alexei; Carsin, Anne-Elie; Kogevinas, Manolis; Schindler, Christian; Lovison, Gianfranco; Herceg, Zdenko; Cuenin, Cyrille; Vermeulen, Roel; Jarvis, Deborah; Amaral, André F.S.; Kronenberg, Florian; Vineis, Paolo; Probst-Hensch, Nicole. 2019. "DNA Methylation in Inflammatory Pathways Modifies the Association between BMI and Adult-Onset Non-Atopic Asthma" Int. J. Environ. Res. Public Health 16, no. 4: 600. https://doi.org/10.3390/ijerph16040600

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