TY - JOUR
T1 - Differential DNA methylation in bronchial biopsies between persistent asthma and asthma in remission
AU - Vermeulen, Cornelis J.
AU - Xu, Cheng Jian
AU - Vonk, Judith M.
AU - ten Hacken, Nick H.T.
AU - Timens, Wim
AU - Heijink, Irene H.
AU - Nawijn, Martijn C.
AU - Boekhoudt, Jeunard
AU - van Oosterhout, Antoon J.
AU - Affleck, Karen
AU - Weckmann, Markus
AU - Koppelman, Gerard H.
AU - van den Berge, Maarten
N1 - Funding Information:
Support statement: Data were generated as part of a Scientific Research Collaboration funded by GSK (COL100037293). The submitted work is co-financed by the Ministry of Economic Affairs and Climate Policy by means of the PPP. Funding information for this article has been deposited with the Crossref Funder Registry.
Funding Information:
Conflict of interest: C.J. Vermeulen reports grants from GSK, during the conduct of the study. C-J. Xu has nothing to disclose. J.M. Vonk has nothing to disclose. N.H.T. ten Hacken has nothing to disclose. W. Timens reports personal fees from Pfizer, GSK, Chiesi, Roche Diagnostics/Ventana, Biotest, Merck Sharp Dohme, Novartis, Lilly Oncology, Boehringer Ingelheim, AstraZeneca, Bristol-Myers-Squibb and AbbVie, and grants from the Dutch Asthma Fund, outside the submitted work. I.H. Heijink has nothing to disclose. M.C. Nawijn reports grants from GSK and the Lung Foundation of the Netherlands, outside the submitted work. J. Boekhoudt has nothing to disclose. A.J. van Oosterhout reports and holds GSK shares. K. Affleck is an employee of GSK and a member of the company share schemes. M. Weckmann has nothing to disclose. G.H. Koppelman reports grants from the Lung Foundation of the Netherlands, TEVA, GSK, Vertex and Ubbo Emmius Foundation, outside the submitted work; and has served on an international advisory board for GSK (money to institution). M. van den Berge reports grants paid to his university from AstraZeneca, TEVA, GSK and Chiesi, outside the submitted work.
Funding Information:
Data were generated as part of a Scientific Research Collaboration funded by GSK (COL100037293). The submitted work is co-financed by the Ministry of Economic Affairs and Climate Policy by means of the PPP. Funding information for this article has been deposited with the Crossref Funder Registry.
Publisher Copyright:
Copyright © ERS 2020
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/2/1
Y1 - 2020/2/1
N2 - Approximately 40% of asthmatics experience remission of asthma symptoms. A better understanding of biological pathways leading to asthma remission may provide insight into new therapeutic targets for asthma. As an important mechanism of gene regulation, investigation of DNA methylation provides a promising approach. Our objective was to identify differences in epigenome wide DNA methylation levels in bronchial biopsies between subjects with asthma remission and subjects with persistent asthma or healthy controls. We analysed differential DNA methylation in bronchial biopsies from 26 subjects with persistent asthma, 39 remission subjects and 70 healthy controls, using the limma package. The comb-p tool was used to identify differentially methylated regions. DNA methylation of CpG-sites was associated to expression of nearby genes from the same biopsies to understand function. Four CpG-sites and 42 regions were differentially methylated between persistent asthma and remission. DNA methylation at two sites was correlated in cis with gene expression at ACKR2 and DGKQ. Between remission subjects and healthy controls 1163 CpG-sites and 328 regions were differentially methylated. DNA methylation was associated with expression of a set of genes expressed in ciliated epithelium. CpGs differentially methylated between remission and persistent asthma identify genetic loci associated with resolution of inflammation and airway responsiveness. Despite the absence of symptoms, remission subjects have a DNA methylation profile that is distinct from that of healthy controls, partly due to changes in cellular composition, with a higher gene expression signal related to ciliated epithelium in remission versus healthy controls.
AB - Approximately 40% of asthmatics experience remission of asthma symptoms. A better understanding of biological pathways leading to asthma remission may provide insight into new therapeutic targets for asthma. As an important mechanism of gene regulation, investigation of DNA methylation provides a promising approach. Our objective was to identify differences in epigenome wide DNA methylation levels in bronchial biopsies between subjects with asthma remission and subjects with persistent asthma or healthy controls. We analysed differential DNA methylation in bronchial biopsies from 26 subjects with persistent asthma, 39 remission subjects and 70 healthy controls, using the limma package. The comb-p tool was used to identify differentially methylated regions. DNA methylation of CpG-sites was associated to expression of nearby genes from the same biopsies to understand function. Four CpG-sites and 42 regions were differentially methylated between persistent asthma and remission. DNA methylation at two sites was correlated in cis with gene expression at ACKR2 and DGKQ. Between remission subjects and healthy controls 1163 CpG-sites and 328 regions were differentially methylated. DNA methylation was associated with expression of a set of genes expressed in ciliated epithelium. CpGs differentially methylated between remission and persistent asthma identify genetic loci associated with resolution of inflammation and airway responsiveness. Despite the absence of symptoms, remission subjects have a DNA methylation profile that is distinct from that of healthy controls, partly due to changes in cellular composition, with a higher gene expression signal related to ciliated epithelium in remission versus healthy controls.
UR - http://www.scopus.com/inward/record.url?scp=85079093467&partnerID=8YFLogxK
U2 - 10.1183/13993003.01280-2019
DO - 10.1183/13993003.01280-2019
M3 - Journal articles
C2 - 31699840
AN - SCOPUS:85079093467
SN - 0903-1936
VL - 55
JO - European Respiratory Journal
JF - European Respiratory Journal
IS - 2
M1 - 1901280
ER -