ISSN 1006-298X      CN 32-1425/R

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肾脏病与透析肾移植杂志 ›› 2018, Vol. 27 ›› Issue (3): 235-239.DOI: 10.3969/j.issn.1006-298X.2018.03.007

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糖尿病肾病患者DNA甲基化表达谱分析

  

  • 出版日期:2018-06-28 发布日期:2018-06-29

DNA methylation profiling in patients with diabetic nephropathy

  • Online:2018-06-28 Published:2018-06-29

摘要:

目的:从表观遗传角度探索糖尿病肾病的发病机制。
方法:收集糖尿病肾病、糖尿病非肾病组、正常对照组的肾组织标本,利用全基因组甲基化测序的方法,分析三组样本之间的甲基化差异,结合转录组的相关信息,分析差异甲基化对糖尿病肾病的影响。
结果:糖尿病肾病患者基因组整体CpG甲基化水平明显高于糖尿病非肾病患者;糖尿病肾病患者与糖尿病非肾病患者之间的差异甲基化区域(differentially methylated regions,DMR)数目高于这两组患者与正常对照之间的DMR数目。对DMR关联到的差异基因进行GO和KEGG功能分析,发现这些差异基因主要和局灶黏连有关,其中,整合素相关基因的甲基化水平在糖尿病肾病患者和糖尿病非肾病患者之间均有显著差异。对DMR的甲基化水平和差异表达基因的表达水平之间的相互关系进行分析,发现90个DMR关联到的62个差异基因的甲基化水平和表达水平之间存在负相关。
结论:糖尿病肾病患者存在明显DNA甲基化差异,DNA甲基化在糖尿病肾病发生发展中可能起重要作用。

关键词: 糖尿病肾病, 全基因组甲基化测序, DNA甲基化

Abstract:

Objective:To explore the epigenetic mechanism of diabetic nephropathy (DN).
Methodology:Nine patients were enrolled into this study. They were divided into  three groups:DN patients,diabetes patients without nephropathy and normal controls.Kidney samples were collected.The difference of methylation level between three groups was analyzed using the method of whole genome bisulfite sequencing.The effects of differential methylation on diabetic nephropathy were investigated by combination with the transcription of kidney tissues of DN.
Results:Global DNA methylation level of CpG was significantly higher in DN patients than in diabetes patients without nephropathy.The number of differentially methylated regions(DMR)between diabetic nephropathy and diabetes without nephropathy was also significantly increased.Results of Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis of genes related with identified DMR showed that focal adhesion was significantly enriched.Methylation levels of integrin family genes of diabetic nephropathy were obviously different from the diabetes without nephropathy.Results of correlation analysis between the methylation levels of DMRs and the expression levels of differentially expressed genes indicated that 90 DMR and 62 related genes had negative correlation with the expression of differentially expressed genes.
Conclusion:
DNA methylation profile was significantly changed in kidneys of diabetic nephropathy.DNA methylation may play a vital role in the pathogenesis of diabetic nephropathy.

Key words: diabetic nephropathy, whole genome bisulfite sequencing, DNA methylation