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

Deanna Baker Frost, Willian da Silveira, 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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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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.

Original languageEnglish
Article number129
Number of pages15
JournalGenes
Volume12
Issue number2
DOIs
Publication statusPublished - 20 Jan 2021

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Keywords

  • African American
  • DNA methylation
  • Genome
  • Skin fibroblasts
  • Systemic sclerosis

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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