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Differential DNA Methylation Landscape in Skin Fibroblasts from African Americans with Systemic Sclerosis

Baker Frost, Deanna; Abraham da Silveira, Willian; Starr Hazard, E.; Atanelishvili, Ilia; C. Wilson, Robert; Flume, Jonathan; L. Day, Kayleigh; C. Oates, James; S. Bogatkevich, Galina; Feghali-Bostwick, Carol; Hardiman, Gary; S. Ramos, Paula

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Authors

Deanna Baker Frost

E. Starr Hazard

Ilia Atanelishvili

Robert C. Wilson

Jonathan Flume

Kayleigh L. Day

James C. Oates

Galina S. Bogatkevich

Carol Feghali-Bostwick

Gary Hardiman

Paula S. Ramos



Abstract

The etiology and reasons underlying the ethnic disparities in systemic sclerosis (SSc) remain unknown. African Americans are disproportionally affected by SSc and yet are underrepresented in research. The aim of this study was to comprehensively investigate the association of DNA methylation levels with SSc in dermal fibroblasts from patients of African ancestry. Reduced representation bisulfite sequencing (RRBS) was performed on primary dermal fibroblasts from 15 SSc patients and 15 controls of African ancestry, and over 3.8 million CpG sites were tested for differential methylation patterns between cases and controls. The dermal fibroblasts from African American patients exhibited widespread reduced DNA methylation. Differentially methylated CpG sites were most enriched in introns and intergenic regions while depleted in 5' UTR, promoters, and CpG islands. Seventeen genes and eleven promoters showed significant differential methylation, mostly in non-coding RNA genes and pseudogenes. Gene set enrichment analysis (GSEA) and gene ontology (GO) analyses revealed an enrichment of pathways related to interferon signaling and mesenchymal differentiation. The hypomethylation of DLX5 and TMEM140 was accompanied by these genes' overexpression in patients but underexpression for lncRNA MGC12916. These data show that differential methylation occurs in dermal fibroblasts from African American patients with SSc and identifies novel coding and non-coding genes.

Citation

Baker Frost, D., Abraham da Silveira, W., Starr Hazard, E., Atanelishvili, I., C. Wilson, R., Flume, J., …S. Ramos, P. (2021). Differential DNA Methylation Landscape in Skin Fibroblasts from African Americans with Systemic Sclerosis. Genes, 12(2), Article 129. https://doi.org/10.3390/genes12020129

Journal Article Type Article
Acceptance Date Jan 18, 2021
Online Publication Date Jan 20, 2021
Publication Date Jan 20, 2021
Deposit Date Oct 25, 2024
Publicly Available Date Oct 25, 2024
Journal Genes
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 12
Issue 2
Article Number 129
DOI https://doi.org/10.3390/genes12020129
PMID 33498390

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