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