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- W4249889669 abstract "Abstract Background Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease whose pathogenesis remains incompletely understood. Increasing evidence suggests that both genetic susceptibilities and changes in DNA methylation influence pivotal biological pathways and thereby contribute to the disease. The role of DNA methylation in SSc has not been fully elucidated, because existing investigations of DNA methylation predominantly focused on nucleotide CpGs within restricted genic regions, and were performed on samples containing mixed cell types. Methods We performed whole-genome bisulfite sequencing on purified CD4+ T lymphocytes from nine SSc patients and nine controls in a pilot study, and then profiled genome-wide cytosine methylation as well as genetic variations. We adopted robust statistical methods to identify differentially methylated genomic regions (DMRs). We then examined pathway enrichment associated with genes located in these DMRs. We also tested whether changes in CpG methylation were associated with adjacent genetic variation. Results We profiled DNA methylation at more than three million CpG dinucleotides genome-wide. We identified 599 DMRs associated with 340 genes, among which 54 genes exhibited further associations with adjacent genetic variation. We also found these genes were associated with pathways and functions that are known to be abnormal in SSc, including Wnt/-catenin signaling pathway, skin lesion formation and progression, and angiogenesis. Conclusion The CD4+ T cell DNA cytosine methylation landscape in SSc involves crucial genes in disease pathogenesis. Some of the methylation patterns are also associated with genetic variation. These findings provide essential foundations for future studies of epigenetic regulation and genome-epigenome interaction in SSc." @default.
- W4249889669 created "2022-05-12" @default.
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- W4249889669 date "2019-08-14" @default.
- W4249889669 modified "2023-10-16" @default.
- W4249889669 title "Whole-genome bisulfite sequencing in systemic sclerosis provides novel targets to understand disease pathogenesis" @default.
- W4249889669 doi "https://doi.org/10.21203/rs.2.12858/v1" @default.
- W4249889669 hasPublicationYear "2019" @default.
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