Common susceptibility loci in both systemic sclerosis and localized scleroderma identified using genetic analysis.
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ABSTRACT:
SUBMITTER: Li Y
PROVIDER: S-EPMC7546879 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
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Common susceptibility loci in both systemic sclerosis and localized scleroderma identified using genetic analysis.
Li Yun Y Wang Wen-Jun WJ Chen Wei-Wei WW Fan Xue X Cao Lu L Xing Ze-Yu ZY Zhen Qi Q Xu Qiong-Qiong QQ Zhu Chen-Yu CY Ge Hui-Yao HY Chen Dian D Zhang Rui-Xue RX Shu Chang C Du Wei W Chen Shi-Rui SR Yuan Xie X Zhang Hui H Hu Xia X Mao Xu-Ming XM Sun Qiu-Ning QN
Chinese medical journal 20201001 19
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Project description:Scleroderma refers to a group of chronic fibrotic immune-mediated diseases of unknown etiology. Characterizing epigenetic changes in childhood-onset scleroderma, systemic sclerosis or localized scleroderma, has not been previously performed. The aim of this study was to assess DNA methylation differences and similarities between juvenile systemic sclerosis (jSSc) and juvenile localized scleroderma (jLS) compared to matched healthy controls. Genome-wide DNA methylation changes in peripheral blood mononuclear cell samples were assessed using the MethylationEPIC array followed by bioinformatic analysis and limited functional assessment. We identified a total of 105 and 144 differentially methylated sites compared to healthy controls in jSSc and jLS, respectively. The majority of differentially methylated sites and genes represented were unique to either jSSc or jLS suggesting a different underlying epigenetic pattern in both diseases. Among shared differentially methylated genes, methylation levels in a CpG site in FGFR2 can distinguish between LS and healthy PBMCs with a high accuracy. Canonical pathway analysis revealed that inflammatory pathways were enriched in genes differentially methylated in jSSc, including STAT3, NF-κB, and IL-15 pathways. In contrast, the HIPPO signaling pathway was enriched in jLS. Our data also suggest a potential role for NOTCH3 in both jSSc and jLS, and revealed a number of transcription factors unique to each of the two diseases. In summary, our data revealed important insights into jSSc and jLS and suggest a potentially novel epigenetic diagnostic biomarker for LS.
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