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

Ayoung Jeong, Medea Imboden, Akram Ghantous, Alexei Novoloaca, Anne-Elie Carsin, Manolis Kogevinas, Christian Schindler, Gianfranco Lovison, Zdenko Herceg, Cyrille Cuenin, Roel Vermeulen, Deborah Jarvis, André F. S. Amaral, Florian Kronenberg, Paolo Vineis and Nicole Probst-Hensch
Additional contact information
Ayoung Jeong: Swiss Tropical and Public Health Institute, 4051 Basel, Switzerland
Medea Imboden: Swiss Tropical and Public Health Institute, 4051 Basel, Switzerland
Akram Ghantous: International Agency for Research on Cancer, 69372 Lyon, France
Alexei Novoloaca: International Agency for Research on Cancer, 69372 Lyon, France
Anne-Elie Carsin: ISGlobal, Barcelona Institute for Global Health, 08003 Barcelona, Spain
Manolis Kogevinas: ISGlobal, Barcelona Institute for Global Health, 08003 Barcelona, Spain
Christian Schindler: Swiss Tropical and Public Health Institute, 4051 Basel, Switzerland
Gianfranco Lovison: Department of Economics, Business and Statistics, University of Palermo, 90128 Palermo, Italy
Zdenko Herceg: International Agency for Research on Cancer, 69372 Lyon, France
Cyrille Cuenin: International Agency for Research on Cancer, 69372 Lyon, France
Roel Vermeulen: Environmental Epidemiology Division, Utrecht University, Institute for Risk Assessment Sciences, 3584CM Utrecht, The Netherlands
Deborah Jarvis: Population Health and Occupational Disease, National Heart and Lung Institute, Imperial College, London SW3 6LR, UK
André F. S. Amaral: Population Health and Occupational Disease, National Heart and Lung Institute, Imperial College, London SW3 6LR, UK
Florian Kronenberg: Division of Genetic Epidemiology, Medical University of Innsbruck, 6020 Innsbruck, Austria
Paolo Vineis: MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK
Nicole Probst-Hensch: Swiss Tropical and Public Health Institute, 4051 Basel, Switzerland

IJERPH, 2019, vol. 16, issue 4, 1-15

Abstract: 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.

Keywords: adult-onset asthma; non-atopic asthma; obesity; inflammation; innate immunity; epigenetics; DNA methylation; epigenome-wide association study (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2019
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