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• W2743256489 abstract "Background Recently, epigenetics has become an important field of research, with several diseases related to alteration in methylation patterns. Whether these epimutations are early events due to a local perturbation causing the initial epigenetic event and then leading to pathogenesis, or a later consequence of the pathology itself remains open for discussion. The objective of this study is to assess the methylation patterns of CpG islands in naive and memory T-cells and monocytes from drug-naive, early Rheumatoid arthritis (RA) patients. Materials and methods The methylation patterns of 480,000 CpGs were measured in 6 healthy controls and 10 RA patients using an Illumina methylation genome-wide array (EWAS). T-tests were used to calculate the significance of the methylation differences at each CpG site. A p-value of 1 × 10–4 was used to elucidate highly specific differences. Methylation patterns of individual promoters were then reconstructed using the Human genome database for the position and length of CpG islands. The genes with 3 or more differentially methylated CpGs clustered over a short distance and localised in potentially regulatory regions of the gene were deemed relevant. Results Analysis of the EWAS data showed 4123 CpG sites differently methylated in naive T-cells, 2672 in memory T-cells and 904 in monocytes. Of the relevant genes, TNFR1 appeared particularly interesting. We therefore focused our next analysis on the TNF-α signalling pathway as this has proven pivotal in early disease. Results highlight 9 genes implicated in the 3 TNF-signalling cascades: TNFR1, LTBR, TRAF1, BCL2, UACA, RNF36, MIR21, DAXX and MAP3K14-AS1. These 9 loci exhibited different methylation patterns in naive T-cells. Each had between 3 and 10 CpGs with differential methylation over short DNA regions ( Conclusion Naive T-cells have been implicated in RA pathogenesis through activation/differentiation by cytokine rather than antigen.1 This data confirms the selective role of naive T-cells in early RA primarily linked to differences in up- and down-regulation of elements involved in the TNF-signalling pathway. Reference Blood, 2002;100:4550–6." @default.
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• W2743256489 date "2017-03-01" @default.
• W2743256489 modified "2023-09-26" @default.
• W2743256489 title "05.03 Differential methylation profile of tnf-signalling genes in t-cells and monocytes" @default.
• W2743256489 doi "https://doi.org/10.1136/annrheumdis-2016-211052.3" @default.
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