دورية أكاديمية
Differential DNA methylation in bronchial biopsies between persistent asthma and asthma in remission.
| العنوان: | Differential DNA methylation in bronchial biopsies between persistent asthma and asthma in remission. |
|---|---|
| المؤلفون: | Vermeulen CJ; Dept of Pulmonary Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands c.j.vermeulen@umcg.nl.; University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, Groningen, The Netherlands., Xu CJ; University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, Groningen, The Netherlands.; Dept of Pediatric Pulmonology and Pediatric Allergology, University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Groningen, The Netherlands.; CiiM & TWINCORE, Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany., Vonk JM; University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, Groningen, The Netherlands.; Dept of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Ten Hacken NHT; Dept of Pulmonary Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.; University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, Groningen, The Netherlands., Timens W; University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, Groningen, The Netherlands.; Dept of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Heijink IH; Dept of Pulmonary Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.; University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, Groningen, The Netherlands.; Dept of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Nawijn MC; University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, Groningen, The Netherlands.; Dept of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Boekhoudt J; Dept of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., van Oosterhout AJ; Allergic Inflammation Discovery Performance Unit, GlaxoSmithKline, Stevenage, UK., Affleck K; Allergic Inflammation Discovery Performance Unit, GlaxoSmithKline, Stevenage, UK., Weckmann M; Dept of Pediatric Pneumology and Allergology, University Medical Center of Schlesswig-Holstein, Airway Research Centre North, Member of the German Centre of Lung Research, Lübeck, Germany., Koppelman GH; University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, Groningen, The Netherlands.; Dept of Pediatric Pulmonology and Pediatric Allergology, University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Groningen, The Netherlands., van den Berge M; Dept of Pulmonary Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.; University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, Groningen, The Netherlands. |
| المصدر: | The European respiratory journal [Eur Respir J] 2020 Feb 06; Vol. 55 (2). Date of Electronic Publication: 2020 Feb 06 (Print Publication: 2020). |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: European Respiratory Society Country of Publication: England NLM ID: 8803460 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 1399-3003 (Electronic) Linking ISSN: 09031936 NLM ISO Abbreviation: Eur Respir J Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Sheffield, United Kingdom : European Respiratory Society Original Publication: Copenhagen : Published jointly by the Society and Munksgaard, 1988- |
| مواضيع طبية MeSH: | Asthma*/genetics , DNA Methylation*, Biopsy ; CpG Islands ; Epigenesis, Genetic ; Humans |
| مستخلص: | 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 i n 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. Competing Interests: Conflict of interest: C.J. Vermeulen reports grants from GSK, during the conduct of the study. Conflict of interest: C-J. Xu has nothing to disclose. Conflict of interest: J.M. Vonk has nothing to disclose. Conflict of interest: N.H.T. ten Hacken has nothing to disclose. Conflict of interest: 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. Conflict of interest: I.H. Heijink has nothing to disclose. Conflict of interest: M.C. Nawijn reports grants from GSK and the Lung Foundation of the Netherlands, outside the submitted work. Conflict of interest: J. Boekhoudt has nothing to disclose. Conflict of interest: A.J. van Oosterhout reports and holds GSK shares. Conflict of interest: K. Affleck is an employee of GSK and a member of the company share schemes. Conflict of interest: M. Weckmann has nothing to disclose. Conflict of interest: 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). Conflict of interest: M. van den Berge reports grants paid to his university from AstraZeneca, TEVA, GSK and Chiesi, outside the submitted work. (Copyright ©ERS 2020.) |
| تواريخ الأحداث: | Date Created: 20191109 Date Completed: 20210621 Latest Revision: 20210621 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1183/13993003.01280-2019 |
| PMID: | 31699840 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1399-3003 |
|---|---|
| DOI: | 10.1183/13993003.01280-2019 |