Analysis of early changes in DNA methylation in synovial fibroblasts of RA patients before diagnosis.

Karouzakis, Emmanuel, Raza, Karim, Kolling, Christoph, Buckley, Christopher D, Gay, Steffen, Filer, Andrew and Ospelt, Caroline (2018) Analysis of early changes in DNA methylation in synovial fibroblasts of RA patients before diagnosis. Scientific reports, 8 (1). p. 7370. ISSN 2045-2322.

[img]
Preview
Text (PDF File Format)
Analysis of early changes in DNA methylation in synovial fibroblasts of RA patients before diagnosis.pdf - Accepted Version
Available under License Creative Commons Attribution 4.0.

Download (1MB) | Preview
Official URL: https://www.nature.com/articles/s41598-018-24240-2

Abstract

DNA methylation is an important epigenetic modification that is known to be altered in rheumatoid arthritis synovial fibroblasts (RASF). Here, we compared the status of promoter DNA methylation of SF from patients with very early RA with SF from patients with resolving arthritis, fully established RA and from non-arthritic patients. DNA was hybridized to Infinium Human methylation 450k and 850k arrays and differential methylated genes and pathways were identified. We could identify a significant number of CpG sites that differed between the SF of different disease stages, showing that epigenetic changes in SF occur early in RA development. Principal component analysis confirmed that the different groups of SF were separated according to their DNA methylation state. Furthermore, pathway analysis showed that important functional pathways were altered in both very early and late RASF. By focusing our analysis on CpG sites in CpG islands within promoters, we identified genes that have significant hypermethylated promoters in very early RASF. Our data show that changes in DNA methylation differ in RASF compared to other forms of arthritis and occur at a very early, clinically yet unspecific stage of disease. The identified differential methylated genes might become valuable prognostic biomarkers for RA development.

Item Type: Article
Subjects: WD Diseases and disorders of systemic, metabolic or environmental origin > WD811 Rheumatology
Divisions: Ambulatory Care > Rheumatology
Related URLs:
Depositing User: Jennifer Manders
Date Deposited: 18 Oct 2019 09:57
Last Modified: 18 Oct 2019 09:57
URI: http://www.repository.uhblibrary.co.uk/id/eprint/2495

Actions (login required)

View Item View Item