Epigenome-wide association study identifies DNA methylation markers for asthma remission in whole blood and nasal epithelium.

Autor: Qi C; Department of Pediatric Pulmonology and Pediatric Allergy, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB, Groningen, the Netherlands.; GRIAC Research Institute, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Vonk JM; GRIAC Research Institute, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.; Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., van der Plaat DA; GRIAC Research Institute, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.; Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Nieuwenhuis MAE; GRIAC Research Institute, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Dijk FN; Department of Pediatric Pulmonology and Pediatric Allergy, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB, Groningen, the Netherlands.; GRIAC Research Institute, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Aïssi D; University Grenoble Alpes, Inserm, CNRS, Team of environmental epidemiology applied to Reproduction and Respiratory health, IAB (Institute for Advanced Biosciences), 38000, Grenoble, France., Siroux V; University Grenoble Alpes, Inserm, CNRS, Team of environmental epidemiology applied to Reproduction and Respiratory health, IAB (Institute for Advanced Biosciences), 38000, Grenoble, France., Boezen HM; GRIAC Research Institute, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.; Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Xu CJ; Research Group of Bioinformatics and Computational Genomics, CiiM, Centre for individualized infection medicine, A Joint Venture Between Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany.; Department of Gastroenterology, Hepatology and Endocrinology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture Between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany.; Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands., Koppelman GH; Department of Pediatric Pulmonology and Pediatric Allergy, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB, Groningen, the Netherlands. g.h.koppelman@umcg.nl.; GRIAC Research Institute, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. g.h.koppelman@umcg.nl.
Jazyk: angličtina
Zdroj: Clinical and translational allergy [Clin Transl Allergy] 2020 Dec 11; Vol. 10 (1), pp. 60. Date of Electronic Publication: 2020 Dec 11.
DOI: 10.1186/s13601-020-00365-4
Abstrakt: 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.
Databáze: MEDLINE
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