DNA Methylation Array Identifies Golli-MBP as a Biomarker for Disease Severity in Childhood Atopic Dermatitis

In this study, we investigated the changes in global methylation status and its functional relevance in childhood atopic dermatitis (AD). Differences in epigenome-scale methylation events in peripheral blood associated with childhood AD were screened using DNA methylation arrays of 24 patients with...

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Bibliographic Details
Published in:Journal of investigative dermatology Vol. 142; no. 1; p. 104
Main Authors: Chen, Kuang-Den, Huang, Ying-Hsien, Guo, Mindy Ming-Huey, Chang, Ling-Sai, Chu, Chi-Hsiang, Bu, Li-Feng, Chu, Chiao-Lun, Lee, Chih-Hung, Liu, Shih-Feng, Kuo, Ho-Chang
Format: Journal Article
Language:English
Published: United States 01.01.2022
Subjects:
Biomarkers
Child, Preschool
Cohort Studies
CpG Islands - genetics
Dermatitis, Atopic - diagnosis
DNA Methylation
Epigenesis, Genetic
Female
High-Throughput Nucleotide Sequencing
Humans
Immunoglobulin E - blood
Male
Myelin Basic Protein - genetics
Severity of Illness Index
Tissue Array Analysis
ISSN:1523-1747, 1523-1747
Online Access:Get more information
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Summary:In this study, we investigated the changes in global methylation status and its functional relevance in childhood atopic dermatitis (AD). Differences in epigenome-scale methylation events in peripheral blood associated with childhood AD were screened using DNA methylation arrays of 24 patients with AD compared with 24 control subjects. Of the 16,840 differentially methylated CpG regions between AD and control subjects, >97% CpG loci revealed hypomethylation in patients with childhood AD. Among the globally hypomethylated loci, we identified two CpG clusters within the golli-mbp locus of the MBP gene, which was functionally enriched by subnetwork enrichment analysis as an orchestrator among associated genes. The differential hypomethylation of the top-ranked cg24700313 cluster in the golli-mbp locus was validated by pyrosequencing in an independent cohort of 224 children with AD and 44 control subjects. DNA methylation was found to be negatively correlated with disease severity but showed no significant correlation with IgE levels after age adjustment. The multivariate correlation analysis represents a higher score in AD intensity with significantly increased IgE levels and decreased methylation levels in cg27400313. We concluded that methylation loss in the golli-mbp locus is an epigenetic factor associated with disease severity of childhood AD.
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ISSN:1523-1747
1523-1747
DOI:10.1016/j.jid.2021.06.025