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

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 esta...

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Autores principales:	Emmanuel Karouzakis, Karim Raza, Christoph Kolling, Christopher D. Buckley, Steffen Gay, Andrew Filer, Caroline Ospelt
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/66ae989f317c47c48a1eb0beaea82838
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spelling	oai:doaj.org-article:66ae989f317c47c48a1eb0beaea828382021-12-02T12:32:09ZAnalysis of early changes in DNA methylation in synovial fibroblasts of RA patients before diagnosis10.1038/s41598-018-24240-22045-2322https://doaj.org/article/66ae989f317c47c48a1eb0beaea828382018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-24240-2https://doaj.org/toc/2045-2322Abstract 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.Emmanuel KarouzakisKarim RazaChristoph KollingChristopher D. BuckleySteffen GayAndrew FilerCaroline OspeltNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-6 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Emmanuel Karouzakis Karim Raza Christoph Kolling Christopher D. Buckley Steffen Gay Andrew Filer Caroline Ospelt Analysis of early changes in DNA methylation in synovial fibroblasts of RA patients before diagnosis
description	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.
format	article
author	Emmanuel Karouzakis Karim Raza Christoph Kolling Christopher D. Buckley Steffen Gay Andrew Filer Caroline Ospelt
author_facet	Emmanuel Karouzakis Karim Raza Christoph Kolling Christopher D. Buckley Steffen Gay Andrew Filer Caroline Ospelt
author_sort	Emmanuel Karouzakis
title	Analysis of early changes in DNA methylation in synovial fibroblasts of RA patients before diagnosis
title_short	Analysis of early changes in DNA methylation in synovial fibroblasts of RA patients before diagnosis
title_full	Analysis of early changes in DNA methylation in synovial fibroblasts of RA patients before diagnosis
title_fullStr	Analysis of early changes in DNA methylation in synovial fibroblasts of RA patients before diagnosis
title_full_unstemmed	Analysis of early changes in DNA methylation in synovial fibroblasts of RA patients before diagnosis
title_sort	analysis of early changes in dna methylation in synovial fibroblasts of ra patients before diagnosis
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/66ae989f317c47c48a1eb0beaea82838
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Analysis of early changes in DNA methylation in synovial fibroblasts of RA patients before diagnosis

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