Shanghai Eye Diseases Prevention & Treatment Center/Shanghai Eye Hospital, No. 380, Kangding Road, Shanghai, 200040, China.
Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Clin Epigenetics. 2020 Jun 3;12(1):77. doi: 10.1186/s13148-020-00871-z.
This study aimed to determine the epigenetic biomarkers of diabetic retinopathy (DR) in subjects with type 2 diabetes mellitus (T2DM). This retrospective study is based on the Shanghai Xinjing community prevention and treatment administrative system of chronic diseases. The subjects enrolled herein were T2DM patients who had undergone long-term follow-up evaluation in the system. Two consecutive studies were conducted. In the discovery cohort, among 19 subjects who had developed DR with a DM duration < 3 years and 21 subjects without DR > 30 years after being diagnosed with DM, an Infinium Human Methylation 850 Beadchip was used to identify differential methylation regions (DMRs) and differential methylation sites (DMSs). The function of the genes was assessed through KEGG enrichment analysis, Gene Ontology (GO) analysis, and pathway network analysis. In the replication cohort, 87 DR patients with a short DM duration and 89 patients without DR over a DM duration > 20 years were compared to assess the association between DMSs and DR upon pyrosequencing.
A total of 34 DMRs were identified. Genes containing DMSs with the top 5 highest beta value differences between DR and non-DR participants were located on chromosome 1 and were present in the S100A13 gene, which was associated with 71 GO terms. Two S100A13 gene sites, i.e., cg02873163 and cg11343894, displayed a good correlation with DR on pyrosequencing.
DMSs in the S100A13 gene may be potential biomarkers of DR.
本研究旨在确定 2 型糖尿病（T2DM）患者糖尿病视网膜病变（DR）的表观遗传生物标志物。本回顾性研究基于上海新泾社区慢性病防治管理系统。本研究纳入的对象为在该系统中接受长期随访评估的 T2DM 患者。进行了两项连续的研究。在发现队列中，在 19 名 DM 病程<3 年且已发展为 DR 的受试者和 21 名 DM 病程>30 年且未发生 DR 的受试者中，使用 Infinium Human Methylation 850 Beadchip 来识别差异甲基化区域（DMR）和差异甲基化位点（DMS）。通过 KEGG 富集分析、基因本体论（GO）分析和通路网络分析评估基因的功能。在复制队列中，比较了 87 名 DM 病程较短且发生 DR 的患者和 89 名 DM 病程较长且未发生 DR 的患者，以评估焦磷酸测序中 DMS 与 DR 之间的关联。
共鉴定出 34 个 DMR。DR 组和非 DR 组间β值差异最大的前 5 个 DMS 所在的基因位于 1 号染色体，存在于 S100A13 基因中，与 71 个 GO 术语相关。S100A13 基因的两个位点，即 cg02873163 和 cg11343894，在焦磷酸测序中与 DR 显示出较好的相关性。
S100A13 基因中的 DMS 可能是 DR 的潜在生物标志物。
