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

Kuang Den Chen; Ying Hsien Huang; Mindy Ming Huey Guo; Ling Sai Chang; Chi Hsiang Chu; Li Feng Bu; Chiao Lun Chu; Chih Hung Lee; Shih Feng Liu; Ho Chang Kuo

doi:10.1016/j.jid.2021.06.025

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

Kuang Den Chen, Ying Hsien Huang, Mindy Ming Huey Guo, Ling Sai Chang, Chi Hsiang Chu, Li Feng Bu, Chiao Lun Chu, Chih Hung Lee, Shih Feng Liu, Ho Chang Kuo^*

^*Corresponding author for this work

School of Medicine

Research output: Contribution to journal › Journal Article › peer-review

10 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	104-113
Number of pages	10
Journal	Journal of Investigative Dermatology
Volume	142
Issue number	1
DOIs	https://doi.org/10.1016/j.jid.2021.06.025
State	Published - 01 2022

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@article{882e872d060040499b770fdc38fc413c,

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

abstract = "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.",

author = "Chen, {Kuang Den} and Huang, {Ying Hsien} and Guo, {Mindy Ming Huey} and Chang, {Ling Sai} and Chu, {Chi Hsiang} and Bu, {Li Feng} and Chu, {Chiao Lun} and Lee, {Chih Hung} and Liu, {Shih Feng} and Kuo, {Ho Chang}",

note = "Publisher Copyright: {\textcopyright} 2021 The Authors",

year = "2022",

month = jan,

doi = "10.1016/j.jid.2021.06.025",

language = "英语",

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AU - Chen, Kuang Den

AU - Huang, Ying Hsien

AU - Guo, Mindy Ming Huey

AU - Chang, Ling Sai

AU - Chu, Chi Hsiang

AU - Bu, Li Feng

AU - Chu, Chiao Lun

AU - Lee, Chih Hung

AU - Liu, Shih Feng

AU - Kuo, Ho Chang

PY - 2022/1

Y1 - 2022/1

N2 - 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.

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

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