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通过基因表达和 DNA 甲基化的综合分析鉴定高血压的潜在诊断生物标志物。

Identification of potential diagnostic biomarkers for hypertension via integrated analysis of gene expression and DNA methylation.

机构信息

Department of Emergency Medicine, Tianjin NanKai Hospital, Tianjin Medical University, Tianjin, China.

Department of Endocrinology and Metabolic Diseases, Tianjin NanKai Hospital, Tianjin Medical University, Tianjin, China.

出版信息

Blood Press. 2024 Aug;33(1):2387025. doi: 10.1080/08037051.2024.2387025. Epub 2024 Aug 31.

DOI:10.1080/08037051.2024.2387025
PMID:39216506
Abstract

OBJECTIVE

Hypertension refers to the elevated blood pressure (BP) in arteries, with a BP reading of 140/90 mm Hg or higher in adults. Over 40% of >25-year-old population have suffered from hypertension. Thus, this study aimed to find novel diagnostic biomarkers for hypertension.

METHODS

All hypertension-related mRNA and methylation datasets were downloaded from the GEO database. Liner model method was used to identify differentially expressed genes (DEGs) between hypertension and control groups. Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes enrichment analysis was employed to obtain functional information. CpG sites and the corresponding genes associated with hypertension were screened using epigenome-wide association study (EWAS) analysis.

RESULTS

There were 37 DEGs between the hypertension group and control group, which were significantly enriched in 84 Biological Process terms, 31 Cellular Component terms, 18 Molecular Function terms and 9 signalling pathways. EWAS results indicated that 1072 CpG sites were associated with hypertension occurrence, corresponding to 1029 genes. After cross-analysis, complement factor D (CFD) and OTU deubiquitinase, ubiquitin aldehyde binding 2 (OTUB2) with methylation modification were identified as diagnostic markers for hypertension.

CONCLUSION

In conclusion, CFD and OTUB2 were potential biomarkers of hypertension occurrence. Our results will provide more information for hypertension diagnosis and would be more reliable combined with multiple biomarkers.

摘要

目的

高血压是指动脉血压升高,成年人血压读数为 140/90mmHg 或更高。超过 40%的>25 岁人群患有高血压。因此,本研究旨在寻找高血压的新型诊断生物标志物。

方法

从 GEO 数据库中下载所有与高血压相关的 mRNA 和甲基化数据集。线性模型方法用于识别高血压组和对照组之间的差异表达基因(DEG)。基因本体论和京都基因与基因组百科全书富集分析用于获取功能信息。使用表观基因组全关联研究(EWAS)分析筛选与高血压相关的 CpG 位点和相应基因。

结果

高血压组和对照组之间有 37 个 DEG,这些基因在 84 个生物过程术语、31 个细胞成分术语、18 个分子功能术语和 9 个信号通路中显著富集。EWAS 结果表明,1072 个 CpG 位点与高血压的发生有关,对应 1029 个基因。经过交叉分析,补体因子 D(CFD)和 OTU 去泛素酶、泛素醛结合 2(OTUB2)的甲基化修饰被确定为高血压的诊断标志物。

结论

综上所述,CFD 和 OTUB2 是高血压发生的潜在生物标志物。我们的结果将为高血压诊断提供更多信息,并与多个生物标志物结合使用将更加可靠。

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