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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Biologically aged females present a distinct symptom and DNA methylation asthma profile.
In: (ATS International Conference Abstracts, 16-21 May 2025, San Francisco). American Thoracic Society, 2025. A5172 - A5172 (Am. J. Respir. Crit. Care Med. ; 211)
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DOI
Introduction Asthma is distinctly sexually dimorphic. Young males
report higher asthma rates than females. This reverses at puberty,
where females present increased incidence, reduced therapeutic
effectiveness and worse asthma symptoms. The underlying molecular
mechanisms causing this remain unknown. Biological DNA methylation
(DNAm) clocks correlate with worse outcomes in chronic diseases such as
asthma. The DNAm profile of males and females with asthma in the context
of DNAm aging (DNAge) is yet to be explored. As such, we aimed to
characterise and explore the DNA methylation profile associated with
DNAge and biological sex in asthma. Methods Nasal brushings from
the paediatric ALLIANCE cohort (n = 46F/74M; asthma = 73/ healthy = 31/
wheeze = 16; avg age = 11 yr range = 3 - 20 yr) were collected and DNAm
processed and analysed by Illumina EPIC array using R software (v4.1; watermelon, minfi).
DNAge was calculated using the established skinHorvath clock. The
association between DNAge, sex, symptom severity or frequency of inhaled
corticosteroid (ICS) use was analysed. Differential methylation
analysis (DMA) comparing pathway enrichment analyses was completed using
R packages (limma, minfi, methylGSA). Differential DNAm significance was determined at a false discovery rate (FDR) < 0.05. Results
Highly symptomatic females with asthma are enriched for an accelerated
DNAge compared to their male counterparts (p = 0.03). DNAge-accelerated
females present increased asthma symptom frequency compared to
DNAge-decelerated females and both male groups (p < 0.0001) despite
equivalent ICS use. Focussing on highly symptomatic asthmatics, DMA
comparing accelerated vs normal DNAged females and males revealed 459
differentially methylated sites (FDR < 0.05). Pathway analysis
reported enrichment for Toll-like receptor, MAPK and Wnt signalling
pathways as well as interferon type I, virus defence and mitochondrial
response pathways (FDR < 0.05). Conclusions Here, we highlight
a unique subset of female asthma patients who experience more asthma
symptoms despite an equivalent use of ICS. In addition, this DNAged
female sub-cohort carries a distinct DNAm profile from the male
counterparts, with enrichment for pathologically relevant signalling and
cellular differentiation pathways. This may present a novel foundation
and support for the use of the DNAge clock as a tool for the
characterisation of asthma patient sub-groups.
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Publikationstyp
Artikel: Konferenzbeitrag
Schlagwörter
Epigenesis
ISSN (print) / ISBN
1073-449X
e-ISSN
1535-4970
Konferenztitel
ATS International Conference Abstracts
Konferzenzdatum
16-21 May 2025
Konferenzort
San Francisco
Quellenangaben
Band: 211,
Heft: Abstracts,
Seiten: A5172 - A5172
Verlag
American Thoracic Society
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Asthma and Allergy Prevention (IAP)
Institute for Allergy Research (IAF)
Institute for Allergy Research (IAF)