Epigenome-wide association study identifies DNA methylation markers for asthma remission in whole blood and nasal epithelium.
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Authors
Qi, CancanVonk, Judith M
van der Plaat, Diana A
Nieuwenhuis, Maartje A E
Dijk, F Nicole
Aïssi, Dylan
Siroux, Valérie
Boezen, H Marike
Xu, Cheng-Jian
Koppelman, Gerard H
Issue Date
2020-12-11
Metadata
Show full item recordAbstract
Background: Asthma is a chronic respiratory disease which is not curable, yet some patients experience spontaneous remission. We hypothesized that epigenetic mechanisms may be involved in asthma remission. Methods: Clinical remission (ClinR) was defined as the absence of asthma symptoms and medication for at least 12 months, and complete remission (ComR) was defined as ClinR with normal lung function and absence of airway hyperresponsiveness. We analyzed differential DNA methylation of ClinR and ComR comparing to persistent asthma (PersA) in whole blood samples (n = 72) and nasal brushing samples (n = 97) in a longitudinal cohort of well characterized asthma patients. Significant findings of whole blood DNA methylation were tested for replication in two independent cohorts, Lifelines and Epidemiological study on the Genetics and Environment of Asthma (EGEA). Results: We identified differentially methylated CpG sites associated with ClinR (7 CpG sites) and ComR (129 CpG sites) in whole blood. One CpG (cg13378519, Chr1) associated with ClinR was replicated and annotated to PEX11 (Peroxisomal Biogenesis Factor 11 Beta). The whole blood DNA methylation levels of this CpG were also different between ClinR and healthy subjects. One ComR-associated CpG (cg24788483, Chr10) that annotated to TCF7L2 (Transcription Factor 7 Like 2) was replicated and associated with expression of TCF7L2 gene. One out of seven ClinR-associated CpG sites and 8 out of 129 ComR-associated CpG sites identified from whole blood samples showed nominal significance (P < 0.05) and the same direction of effect in nasal brushes. Conclusion: We identified DNA methylation markers possibly associated with clinical and complete asthma remission in nasal brushes and whole blood, and two CpG sites identified from whole blood can be replicated in independent cohorts and may play a role in peroxisome proliferation and Wnt signaling pathway.Citation
Clin Transl Allergy. 2020 Dec 11;10(1):60. doi: 10.1186/s13601-020-00365-4.Affiliation
CiiM, Zentrum für individualisierte Infektionsmedizin, Feodor-Lynen-Str.7, 30625 Hannover.Publisher
BMCPubMed ID
33303027Type
ArticleLanguage
enISSN
2045-7022ae974a485f413a2113503eed53cd6c53
10.1186/s13601-020-00365-4
Scopus Count
The following license files are associated with this item:
- Creative Commons
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