Nasal DNA Methylation is Associated with Childhood Asthma

Zhang, Xue; Myers, Jocelyn M. Biagini; Burleson, J D; Ulm, Ashley; Bryan, Kelly S; Rothenberg, Marc E.; Weirauch, Matthew T.; Baker, Theresa; Kovacic, Melinda S. Butsch; Ji, Hong

doi:10.2217/epi-2017-0127

Cited by 34 publications

(54 citation statements)

References 68 publications

(56 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Three studies investigating the genome‐wide methylation of nasal epithelial cells in asthmatics have been published: the first by Yang et al in 2017 and two studies in 2018 by Forno et al and Zhang et al, respectively …”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…Zhang et al studied differential methylation in 29 African American sibling pairs discordant for asthma. Six CpGs were identified as differentially methylated, but only achieved nominal significance . Only one CpG, cg14830002, was externally replicated in two other asthma cohorts, and the authors validated three of the CpGs in a larger cohort of 54 sibling pairs using pyrosequencing …”

Section: Resultsmentioning

confidence: 99%

“…Six CpGs were identified as differentially methylated, but only achieved nominal significance. 50 Only one CpG, cg14830002, was externally replicated in two other asthma cohorts, and the authors validated three of the CpGs in a larger cohort of 54 sibling pairs using pyrosequencing. 50 Forno et al 32 studied differential methylation in a cohort of 483…”

Section: F I G U R E 3 Pathway and Gene Interactions Network For A Sementioning

confidence: 99%

See 3 more Smart Citations

Epigenome‐wide association studies in asthma: A systematic review

Edris

Dekker

Melén

et al. 2019

Clin Experimental Allergy

View full text Add to dashboard Cite

Objective Asthma is a common chronic respiratory airway disease influenced by environmental factors and possibly their interaction with the human genome causing epigenetic changes. Epigenome‐wide association studies (EWAS) have mainly investigated DNA methylation and its association with disease or traits, exposure factors or gene expression. This systematic review aimed to identify all EWAS assessing differentially methylated sites associated with asthma in humans. Design Structured systematic literature search following PRISMA guidelines, Newcastle‐Ottawa Scale (NOS) for cohort studies was used for bias assessment. Data Sources We searched PubMed and Embase databases from 2005 to 2019. Eligibility Criteria Epigenome‐wide association studies testing association between differential methylation and asthma in humans. Results Overall, we identified 16 EWAS studies complying with our search criteria. Twelve studies were conducted on children, and 10 were conducted on sample sizes <150 subjects. Four hundred and nineteen CpGs were reported in children studies after correction for multiple testing. In the adult studies, thousands of differentially methylated sites were identified. Differential methylation in inflammatory‐related genes correlated with higher levels of gene expressions of inflammatory modulators in asthma. Differentially methylated genes associated with asthma included SMAD3, SERPINC1, PROK1, IL13, RUNX3 and TIGIT. Forty‐one CpGs were replicated at least once in blood samples, and 28 CpGs were replicated in nasal samples. Conclusion Although many differentially methylated CpGs in genes known to be involved in asthma have been identified in EWAS to date, we conclude that further studies of larger sample sizes and analyses of differential methylation between different phenotypes are needed in order to comprehensively evaluate the role of epigenetic factors in the pathophysiology and heterogeneity of asthma, and the potential clinical utility to predict or classify patients with asthma.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: F I G U R E 3 Pathway and Gene Interactions Network For A Sementioning

confidence: 99%

See 2 more Smart Citations

Epigenome‐wide association studies in asthma: A systematic review

Edris

Dekker

Melén

et al. 2019

Clin Experimental Allergy

View full text Add to dashboard Cite

show abstract

“…The nasal epithelium is considered a noninvasive proxy for bronchial epithelium in children, 6,7 and it has been used as target tissue to study asthma. 8,25 However, rhinitis is highly prevalent and shows comorbidity and shared genetic origins with asthma. 10,11,26 Taking the shared mechanisms of asthma and rhinitis into consideration, we used a combined phenotype of asthma and rhinitis (AsRh).…”

Section: Discussionmentioning

confidence: 99%

Nasal DNA methylation profiling of asthma and rhinitis

Jiang

Yang

et al. 2020

Journal of Allergy and Clinical Immunology

View full text Add to dashboard Cite

Background: Epigenetic signatures in the nasal epithelium, which is a primary interface with the environment and an accessible proxy for the bronchial epithelium, might provide insights into mechanisms of allergic disease. Objective: We aimed to identify and interpret methylation signatures in nasal epithelial brushes associated with rhinitis and asthma. Methods: Nasal epithelial brushes were obtained from 455 children at the 16-year follow-up of the Dutch Prevention and Incidence of Asthma and Mite Allergy birth cohort study. Epigenome-wide association studies were performed on children with asthma, rhinitis, and asthma and/or rhinitis (AsRh) by using logistic regression, and the top results were replicated in 2 independent cohorts of African American and Puerto Rican children. Significant CpG sites were related to environmental exposures (pets, active and passive smoking, and molds) during secondary school and were correlated with gene expression by RNA-sequencing (n 5 244).

show abstract

DNA methylation biomarkers in asthma and rhinitis: Are we there yet?

Legaki

Arsenis

Τaka

et al. 2022

Clinical & Translational All

View full text Add to dashboard Cite

The study of epigenetics has improved our understanding of mechanisms underpinning gene‐environment interactions and is providing new insights in the pathophysiology of respiratory allergic diseases. We reviewed the literature on DNA methylation patterns across different tissues in asthma and/or rhinitis and attempted to elucidate differentially methylated loci that could be used to characterize asthma or rhinitis. Although nasal and bronchial epithelia are similar in their histological structure and cellular composition, genetic and epigenetic regulation may differ across tissues. Advanced methods have enabled comprehensive, high‐throughput methylation profiling of different tissues (bronchial or nasal epithelial cells, whole blood or isolated mononuclear cells), in subjects with respiratory conditions, aiming to elucidate gene regulation mechanisms and identify new biomarkers. Several genes and CpGs have been suggested as asthma biomarkers, though research on allergic rhinitis is still lacking. The most common differentially methylated loci presented in both blood and nasal samples are ACOT7, EPX, KCNH2, SIGLEC8, TNIK, FOXP1, ATPAF2, ZNF862, ADORA3, ARID3A, IL5RA, METRNL and ZFPM1. Overall, there is substantial variation among studies, (i.e. sample sizes, age groups and disease phenotype). Greater variability of analysis method detailed phenotypic characterization and age stratification should be taken into account in future studies.

show abstract

Nasal DNA Methylation is Associated with Childhood Asthma

Abstract: We identified novel DNAm variations associated with childhood asthma and suggested new disease-contributing epigenetic mechanisms.

Cited by 34 publications

References 68 publications

Epigenome‐wide association studies in asthma: A systematic review

Epigenome‐wide association studies in asthma: A systematic review

Nasal DNA methylation profiling of asthma and rhinitis

DNA methylation biomarkers in asthma and rhinitis: Are we there yet?

Contact Info

Product

Resources

About