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DNA methylation in inflammatory pathways modifies the association between BMI and adult-onset non-atopic asthma

Jeong, Ayoung and Imboden, Medea and Ghantous, Akram and Novoloaca, Alexei and Carsin, Anne-Elie and Kogevinas, Manolis and Schindler, Christian and Lovison, Gianfranco and Herceg, Zdenko and Cuenin, Cyrille and Vermeulen, Roel and Jarvis, Deborah and Amaral, André F. S. and Kronenberg, Florian and Vineis, Paolo and Probst-Hensch, Nicole. (2019) DNA methylation in inflammatory pathways modifies the association between BMI and adult-onset non-atopic asthma. International journal of environmental research and public health, 16 (4). p. 600.

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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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Chronic Disease Epidemiology > Genetic Epidemiology of Non-Communicable Diseases (Probst-Hensch)
03 Faculty of Medicine > Departement Public Health > Sozial- und Präventivmedizin > Genetic Epidemiology of Non-Communicable Diseases (Probst-Hensch)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Biostatistics > Biostatistics Frequentist Modelling
UniBasel Contributors:Imboden, Medea and Jeong, Ayoung and Schindler, Christian and Probst Hensch, Nicole
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:1660-4601
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:12 Mar 2019 08:45
Deposited On:12 Mar 2019 08:45

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