Epigenome-wide association study identifies DNA methylation markers for asthma remission in whole 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 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.

Genome-Wide DNA Methylation Profile in Whole Blood of Patients With Chronic Spontaneous Urticaria

“…We compared our result of the 439 DMPs and the 304 DMGs with previous studies of DNA methylation in whole blood of other allergies or IgE-driven diseases. CpG cg24788483 that annotated to transcription factor 7-like 2 (TCF7L2) was reported to be related to complete remission of asthma (48). The TCF7L2 gene product is a transcription factor that plays a role in the Wnt signaling pathway (49) (51).…”

Aging Regulates Post-Viral Asthmatic Airway Pathology

“…Recently, molecular biomarkers of pediatric asthma remission have garnered increased attention with one genome-wide and one epigenome-wide association study published so far 57,58 . Importantly, these studies identi ed a polymorphism in the IL-33 receptor IL1R1 that was associated with asthma remission by adulthood 58 .…”

Omics technologies in allergy and asthma research: An EAACI position paper

“… 28 , 29 Several recent, epigenomic studies in the field of allergic diseases allowed identification of epigenetic signatures of asthma/allergy and are summarized in Table S2 . 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 Additionally, epigenetic mechanisms involved in the development, course, and control of allergic diseases are in detail reviewed elsewhere. 29 , 47 , 58 , 59 , 60 , 61 …”

“… 69 However, methylation profiling microarrays are the most frequently used technology in the allergic diseases research field (Table S2 ). 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 Notably, the recent development of the CRISP/Cas9 technology provides a powerful editing and control toolbox for obtaining a better understanding of epigenetic mechanisms. 47 , 70 For a broad overview of all available approaches in epigenetics, refere to the mentioned references.…”