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Epigenome-wide association study identifies DNA methylation markers for asthma remission in blood and nasal epithelium
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  • Cancan Qi,
  • Judith Vonk,
  • Diana A. van der Plaat,
  • Maartje Nieuwenhuis,
  • Nicole Dijk,
  • Dylan Aïssi,
  • Valérie SIROUX,
  • H. Boezen,
  • Chengjian Xu,
  • Gerard Koppelman
Cancan Qi
University Medical Center Groningen
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Judith Vonk
University of Groningen, University Medical Center Groningen
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Diana A. van der Plaat
University of Groningen, University Medical Center Groningen
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Maartje Nieuwenhuis
University of Groningen, University Medical Center Groningen, GRIAC Research Institute
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Nicole Dijk
University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital
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Dylan Aïssi
Université de Grenoble
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Valérie SIROUX
Université de Grenoble
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H. Boezen
University of Groningen, University Medical Center Groningen
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Chengjian Xu
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
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Gerard Koppelman
University Medical Center Groningen
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Abstract

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 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.