Cell-specific epigenome-wide DNA methylation profile in long-term cultured minor salivary gland epithelial cells from patients with Sjogren's syndrome
Cell-specific epigenome-wide DNA methylation profile in long-term cultured minor salivary gland epithelial cells from patients with Sjogren's syndrome
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DOI：
10.1136/annrheumdis-2016-210167
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发表时间：
2017-03-01
影响因子：
27.4
通讯作者：
Renaudineau, Yves
中科院分区：
文献类型：
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作者：
Charras, Amandine;Konsta, Orsia D.;Renaudineau, Yves
目的原发性干燥综合征（pSS），又称自身免疫性上皮病，其病因学尚不完全清楚，但包括表观遗传学的贡献。因此，本研究的目的是研究唾液腺上皮细胞（SGEC）中的DNA甲基化，并将结果与公开的pSS B和T细胞的结果进行比较。方法选择长期培养的SGEC进行表观基因组全关联研究（EWAS）使用来自Illumina的HumanMethylation 450 K阵列对pSS患者与对照进行比较。（DMC）共发现SGEC中4662个位点，对应2560个基因，575个基因有两个或两个以上DMC位点（DMC）。进一步的分析强调了干扰素调节基因的重要比例（61%），钙通道（低甲基化）和Wnt通道（高甲基化）。当比较SGEC与pSS T和/或B细胞结果时，观察到差异甲基化基因的重要重叠（38.8%）和pSS危险因素（71.4%），结论在SGEC中进行的这项研究强调了DNA甲基化在pSS发病机制中的作用，并支持在未来的EWAS研究中进行纯细胞分析的必要性，分析pSS患者的唾液腺。
Objectives The aetiology of primary Sjogren's syndrome (pSS), also referred to as autoimmune epithelitis, is incompletely understood but includes an epigenetic contribution. Accordingly, the aim of this study was to investigate DNA methylation in salivary gland epithelial cells (SGEC), and to compare results with those publicly available from pSS B and T cells.Methods Long-term cultured SGEC were selected to conduct an epigenome-wide association study (EWAS) in patients with pSS with comparison to controls using the HumanMethylation 450 K array from Illumina.Results The analysis of differentially methylated CpG (DMC) uncovered 4662 positions corresponding to 2560 genes, and 575 genes with two or more DMC sites (DMCs), in SGEC as compared with controls. Further analysis highlighted an important proportion of interferon-regulated genes (61%), the calcium pathway (hypomethylated) and the Wnt pathway (hypermethylated). When comparing SGEC with pSS T and/or B cell results, an important overlap was observed with respect to differentially methylated genes (38.8%) and pSS risk factors (71.4%), although such assertion was not true when comparing DMCs.Conclusions This study conducted in SGEC emphasises the role of DNA methylation in pSS pathogenesis and supports the necessity to conduct pure cell analysis for future EWAS studies when analysing salivary glands from patients with pSS.