4.6 Article

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

期刊

GENES
卷 12, 期 2, 页码 -

出版社

MDPI
DOI: 10.3390/genes12020129

关键词

systemic sclerosis; African American; DNA methylation; genome; skin fibroblasts

资金

  1. US National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (NIH) [T32 AR050958, K01 AR067280, P30 AR072582, R03 AR065801, P60 AR062755, K24 AR060297]
  2. US National Institute on Drug Abuse of the NIH [U01 DA045300, U54 MD010706-CHH]
  3. US National Cancer Institute of the NIH [P30 CA138313]
  4. National Center for Advancing Translational Sciences of the NIH [KL2 TR001452, UL1 TR001450]
  5. MUSC Center for Genomic Medicine
  6. Scleroderma Foundation
  7. Queens University Belfast

向作者/读者索取更多资源

This study found widespread hypomethylation in dermal fibroblasts from African American patients with SSc, with enrichment of genes and pathways related to interferon signaling and mesenchymal differentiation, indicating potential new targets for further research.
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.

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