DNA Methylation in Inflammatory Pathways Modifies the Association between BMI and Adult-Onset Non-Atopic Asthma
Year: 2019
Type: article
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.
Institutions: Swiss Tropical and Public Health Institute, University of Basel, Centre international de recherche sur le cancer, Universitat Pompeu Fabra, Barcelona Institute for Global Health, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, University of Palermo, Utrecht University, Imperial College London, Innsbruck Medical University, Universität Innsbruck, Public Health England, Italian institute for Genomic Medicine, MRC Centre for Environment and Health
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,824
Awards: G1069568936, SAPALDIA COHORT STUDY: Impact of environmental and personal risk factors on the occurrence, course, remission and progression of respiratory disease in the swiss population-data analysis, MRC-PHE Centre for Environment and Health, SAPALDIA COHORT STUDY: Impact of air pollution on the cardiovascular and respiratory system in the Swiss population, SAPALDIA Cohort on Healthy Aging, G2837121351, The SAPALDIA II Cohort Study:Impact of environmental and personalrisk factors on the occurrence, course, remission and progressionof respiratory diseases in the Swiss population., Swiss Study on Air Pollution and Lung Diseases in Adults: Mortality follow-up extension., G3540089817, G3708726189, Swiss study on air pollution and lung diseases in adults (SAPALDIA study), Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA), Air Pollution Exposure Assessment in Eight Swiss Areas, G5454627851, The SAPALDIA II Cohort Study:Impact of environmental and personalrisk factors on the occurrence, course, remission and progressionof respiratory diseases in the Swiss population., Swiss Study on Air Pollution and Lung Diseases in Adults: Participants'Follow-up and Further Analysis., G612785983, G6277104061, G6903841720, G8281345491, SAPALDIA COHORT STUDY: Mortality follow-up, maintenance of the cohort, the biobanks and the data bases.
OpenAlex ID: W2911524176