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Aberrant Promoter Hypomethylation of Sortilin 1: A Moyamoya Disease Biomarker

Title
Aberrant Promoter Hypomethylation of Sortilin 1: A Moyamoya Disease Biomarker
Authors
Sung, Hye YounLee, Ji YeounPark, Ae KyungMoon, Youn JooJo, InhoPark, Eun-MiWang, Kyu-ChangPhi, Ji HoonAhn, Jung-HyuckKim, Seung-Ki
Ewha Authors
박은미조인호안정혁성혜윤
SCOPUS Author ID
박은미scopus; 조인호scopusscopus; 안정혁scopus; 성혜윤scopus
Issue Date
2018
Journal Title
JOURNAL OF STROKE
ISSN
2287-6391JCR Link

2287-6405JCR Link
Citation
JOURNAL OF STROKE vol. 20, no. 3, pp. 350 - +
Keywords
Moyamoya diseaseDNA methylationBiomarkersDiagnosisSortilin 1
Publisher
KOREAN STROKE SOC
Indexed
SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Background and Purpose The pathogenesis of moyamoya disease (MMD) remains poorly understood, and no reliable molecular biomarkers for MMD have been identified to date. The present study aimed to identify epigenetic biomarkers for use in the diagnosis of MMD. Methods We performed integrated analyses of gene expression profiles and DNA methylation profiles in endothelial colony forming cells (ECFCs) from three patients with MMD and two healthy individuals. Candidate gene mRNA expression and DNA methylation status were further validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and pyrosequencing analysis of an expanded ECFC sample set from nine patients with MMD and ten controls. We evaluated the diagnostic accuracy of the potential biomarkers identified here using receiver operating characteristic curve analyses and further measured major angiogenic factor expression levels using a tube formation assay and RT-qPCR. Results Five candidate genes were selected via integrated analysis; all five were upregulated by hypomethylation of specific promoter CpG sites. After further validation in an expanded sample set, we identified a candidate biomarker gene, sortilin 1 (SORT1). DNA methylation status at a specific SORT1 promoter CpG site in ECFCs readily distinguished patients with MMD from the normal controls with high accuracy (area under the curve 0.98, sensitivity 83.33%, specificity 100%). Furthermore, SORT1 overexpression suppressed endothelial cell tube formation and modulated major angiogenic factor and matrix metalloproteinase-9 expression, implying SORT1 involvement in MMD pathogenesis. Conclusions Our findings suggest that DNA methylation status at the SORT1 promoter CpG site may be a potential biomarker for MMD.
DOI
10.5853/jos.2018.00962
Appears in Collections:
의과대학 > 의학과 > Journal papers
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