Dynamic DNA methylation of EPHX2 in diabetic kidney disease progression: A potential biomarker

IF 1 Q4 GENETICS & HEREDITY

Gene Reports Pub Date : 2025-05-02 DOI:10.1016/j.genrep.2025.102245

Guoxiong Deng , Ziyi Feng , Xiaomu Kong , Peng Gao , Yongwei Jiang , Yi Liu , Meimei Zhao , LiangMa

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引用次数: 0

Abstract

Subject

To explore the correlation between the methylation level of EPHX2 gene with diabetic kidney disease (DKD).

Methods

We conducted a case-control study contained 50 pairs of DKD and diabetes mellitus (DM) patients. CpG sites of EPHX2 gene around transcription start site are detected using mass spectrometry combined with bisulfite conversation.

Result

Significant differences were found in the methylation of EPHX2 site 1 (13.59 % vs 19.30 %, P = 0.001), 4(52.81 % vs. 45.2 %, P < 0.001) and 7(41.71 % vs. 48.00 %, P < 0.001) between DKD and diabetes mellitus (DM) patients. Logistic regression showed that for every 1 % increase in site 7 methylation, the risk of DN increased by 56 % (OR = 1.56, 95 %CI:1.26–1.93), suggesting its potential as an independent risk factor. The ROC curve shows that the methylation level of site1,7 have great performance to distinguish DKD and DM (AUC = 0.896, Sensitivity: 91.8 %, specificity: 84.4 %).

Conclusion

The DNA methylation levels of EPHX2 gene are associated with the occurrence and development of DKD. In addition, changes in DNA methylation levels at sites 1 and 7 of the EPHX2 gene may serve as potential biomarkers for the diagnosis of DKD and indicate new strategy to delay the progress of DKD.

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EPHX2在糖尿病肾病进展中的动态DNA甲基化：一个潜在的生物标志物

目的探讨EPHX2基因甲基化水平与糖尿病肾病（DKD）的相关性。方法对50对糖尿病合并糖尿病（DM）患者进行病例对照研究。采用质谱联用亚硫酸盐对话法检测EPHX2基因转录起始位点附近的CpG位点。结果EPHX2位点1甲基化（13.59%比19.30%,P = 0.001）、4甲基化(52.81%比45.2%,P <；0.001)和7(41.71%比48.00%,P <；0.001)， DKD与糖尿病（DM）患者之间存在差异。Logistic回归显示，位点7甲基化每增加1%，DN的风险增加56% (OR = 1.56, 95% CI: 1.26-1.93)，提示其可能是一个独立的危险因素。ROC曲线显示，site1,7的甲基化水平对区分DKD和DM有很好的效果（AUC = 0.896，灵敏度：91.8%，特异性：84.4%）。结论EPHX2基因的DNA甲基化水平与DKD的发生发展有关。此外，EPHX2基因1和7位点DNA甲基化水平的变化可能作为DKD诊断的潜在生物标志物，并提示延迟DKD进展的新策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Gene Reports Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.30

自引率

7.70%

发文量

246

审稿时长

49 days

期刊介绍： Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.