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

被引：11

作者：

Chen, Kuang-Den ^{[1
,2
,3
,4
,5
,6
]}

Huang, Ying-Hsien ^{[1
,2
,3
]}

Guo, Mindy Ming-Huey ^{[1
,2
,3
]}

Chang, Ling-Sai ^{[1
,2
,3
]}

Chu, Chi-Hsiang ^{[7
,8
]}

Bu, Li-Feng ^{[2
,4
,5
,6
]}

Chu, Chiao-Lun ^{[1
,2
,3
]}

Lee, Chih-Hung ^{[9
]}

Liu, Shih-Feng ^{[2
,10
,11
]}

Kuo, Ho-Chang ^{[1
,2
,3
,10
,11
]}

机构：

[1] Kaohsiung Chang Gung Mem Hosp, Dept Pediat, Kaohsiung, Taiwan

[2] Chang Gung Univ, Coll Med, Kaohsiung, Taiwan

[3] Kaohsiung Chang Gung Mem Hosp, Kawasaki Dis Ctr, Kaohsiung, Taiwan

[4] Kaohsiung Chang Gung Mem Hosp, Inst Translat Res Biomed, Kaohsiung, Taiwan

[5] Kaohsiung Chang Gung Mem Hosp, Liver Transplantat Ctr, Kaohsiung, Taiwan

[6] Kaohsiung Chang Gung Mem Hosp, Dept Surg, Kaohsiung, Taiwan

[7] Natl Cheng Kung Univ, Dept Stat, Tainan, Taiwan

[8] Natl Univ Kaohsiung, Inst Stat, Kaohsiung, Taiwan

[9] Kaohsiung Chang Gung Mem Hosp, Dept Dermatol, Kaohsiung, Taiwan

[10] Kaohsiung Chang Gung Mem Hosp, Dept Internal Med, Div Pulm & Crit Care Med, Kaohsiung, Taiwan

[11] Kaohsiung Chang Gung Mem Hosp, Dept Resp Therapy, Kaohsiung, Taiwan

来源：

JOURNAL OF INVESTIGATIVE DERMATOLOGY | 2022年 / 142卷 / 01期

关键词：

MYELIN BASIC-PROTEIN; GENE-EXPRESSION; MAST-CELLS; IGE; EPIGENETICS; FILAGGRIN; COMORBIDITIES; EOSINOPHILS; PROMOTER; LINEAGE;

D O I：

10.1016/j.jid.2021.06.025

中图分类号：

R75 [皮肤病学与性病学];

学科分类号：

100206 ;

摘要：

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.

引用

页码：104 / 113

页数：10

共 52 条

[31] Th2 lineage commitment and efficient IL-4 production involves extended demethylation of the IL-4 gene [J].