激素敏感型及依赖型肾病综合征患儿基因甲基化研究及其生物信息学分析

发布时间：2018-08-22 10:36

【摘要】：目的目前关于激素敏感型肾病综合征(SSNS)及激素依赖型肾病综合征(SDNS)患儿的基因甲基化研究较少,文中旨在筛选SSNS和SDNS甲基化差异表达的基因,并进行生物信息学分析,探讨可能的发病机制及寻找潜在的治疗靶标。方法选择2015年1月至12月在南京军区南京总医院儿科住院患者7例,SSNS者(n=3):泼尼松足量[2 mg/(kg·d)或60mg/(m2·d)]治疗,4周内尿蛋白转阴者;SDNS者(n=4):对激素治疗敏感,但是连续2次减药或停药2周内复发者。分别提取2组患儿的外周血DNA,利用基因甲基化芯片技术筛选差异表达的甲基化基因,并对其进行生物信息学对检测结果进行分析。结果甲基化芯片结果发现,与SSNS组比较,SDNS组存在318个差异甲基化基因,其中有193个基因表达为高甲基化,125个为低甲基化;这些异常基因主要位于DNA的开放阅读框和Cp G岛区域。甲基化差异基因主要涉及Rho鸟嘌呤核苷酸交换因子活性、核苷三磷酸酶调节活性、GTP酶调节活性等分子功能。生物学过程方面主要涉及调节前体代谢产物和能量、抗原加工提呈、Rho及Ras蛋白信号传导通路、伪足集合、再生等生物过程。在细胞组成方面,主要涉及MHC蛋白复合物、染色质周纤维及MHC 1类分子的蛋白复合物。通过KEGG信号通路分析发现,差异基因主要参与9个信号通路,其中主要涉及I型糖尿病、淀粉与蔗糖的代谢、同种异体移植物的排斥和自身免疫性甲状腺病等信号通路。结论广泛存在的SDNS患儿基因异常甲基化现象,为激素依赖的原因之一,这为寻找潜在的治疗靶标提供了依据。
[Abstract]:Objective there are few studies on gene methylation in children with hormone sensitive nephrotic syndrome (SSNS) and steroid-dependent nephrotic syndrome (SDNS). The purpose of this study was to screen the differentially expressed genes between SSNS and SDNS and to make bioinformatics analysis. To explore the possible pathogenesis and search for potential therapeutic targets. Methods from January to December 2015, 7 inpatients with SSNs in Nanjing General Hospital of Nanjing military region were treated with prednisone [2 mg/ (kg d) or 60mg/ (m2 d)] for 4 weeks. However, two consecutive drug reduction or withdrawal within 2 weeks of recurrence. The DNA of peripheral blood was extracted from two groups of children. The differentially expressed methylated genes were screened by gene methylation microarray, and the results were analyzed by bioinformatics. Results the results of methylation microarray showed that there were 318 differentially methylated genes in SSNS group, among which 193 were hypermethylated and 125 were hypomethylated. These abnormal genes were mainly located in the open reading frame and CP G island region of DNA. Methylation differential genes are mainly involved in the activities of Rho guanine nucleotide exchange factor, nucleoside triphosphatase regulating activity and so on. Biological processes are mainly involved in the regulation of precursor metabolites and energy, antigen processing and presentation of Rho and Ras protein signal transduction pathways, pseudopodia collection, regeneration and other biological processes. In cell composition, MHC protein complex, perichromatin fiber and MHC class 1 protein complex are involved. KEGG signaling pathway analysis showed that differential genes were involved in 9 signaling pathways, including type I diabetes mellitus, metabolism of starch and sucrose, allograft rejection and autoimmune thyroid disease. Conclusion the abnormal methylation of SDNS gene is one of the causes of hormone dependence in children with SDNS, which provides a basis for searching for potential therapeutic targets.
【作者单位】：南方医科大学金陵医院(南京军区南京总医院)儿科;
【基金】：国家自然科学基金(81270800)
【分类号】：R726.9

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