Dataset Information

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

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-?B 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.

SUBMITTER: Jeong A

PROVIDER: S-EPMC6406386 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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

Jeong Ayoung A Imboden Medea M Ghantous Akram A Novoloaca Alexei A Carsin Anne-Elie AE Kogevinas Manolis M Schindler Christian C Lovison Gianfranco G Herceg Zdenko Z Cuenin Cyrille C Vermeulen Roel R Jarvis Deborah D Amaral André F S AFS Kronenberg Florian F Vineis Paolo P Probst-Hensch Nicole N

International journal of environmental research and public health 20190219 4

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 Pollu ...[more]

PMID: 30791383

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Project description:Studies of asthma phenotypes have identified obesity as a component of a group characterized by a high proportion of subjects with adult-onset asthma. However, whether age of asthma onset modifies the association between obesity and asthma is unknown.We sought to compare the associations between body mass index (BMI) categories with physiological, inflammatory, and clinical parameters across age of asthma onset phenotypes; and to compare the rate of BMI change in relation to asthma duration, by age of onset asthma phenotypes.From the Severe Asthma Research Program, we defined age of asthma onset as early (<12 years of age) and late (?12 years of age). Comparisons of BMI categories were done within age-of-onset groups, and obesity was also compared across these groups. Multivariable logistic regression analysis was done to evaluate the association between BMI categories with health care use and respiratory symptoms and multivariable linear regression for the association between duration of asthma and weight gain (BMI change per year). An interaction between obesity and age of asthma onset was included in the multivariable analyses.The study population consisted of 1049 subjects, and the median age for asthma onset was 10 years (interquartile range, 4-25 years); 48% had late-onset asthma (?12 years of age), and 52% had early-onset asthma (<12 years of age). Compared with obese subjects with late-onset asthma, obese subjects with early-onset asthma had more airway obstruction, bronchial hyperresponsiveness, and higher odds ratios of ever having 3 or more previous oral steroid tapers per year or intensive care unit admissions for asthma per preceding year (interactions between obesity and age of asthma onset were P = .055 and P = .02, respectively). In subjects with early-onset asthma but not in subjects with late-onset asthma, there was a significant association between increasing BMI and duration of asthma after adjusting for confounders. The interaction between asthma duration and age of asthma onset was a P value of less than .01.Asthmatic subjects are differentially affected by obesity based on whether they had asthma early (<12 years of age) or later in life. These results highlight the need to understand obesity as a comorbidity that affects specific clinical phenotypes and not all asthma subjects alike.

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Dataset Information

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

Publications

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

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