转录组学测序解析难治性高血压基因表达特征及核心差异基因

doi:10.16288/j.yczz.25-104

遗传 ›› 2026, Vol. 48 ›› Issue (1): 76-86.doi: 10.16288/j.yczz.25-104

转录组学测序解析难治性高血压基因表达特征及核心差异基因

姜彤¹(), 彭世靖¹, 王姗姗¹, 王昱琪², 赵文杰¹, 杨雯晴¹()

1.山东中医药大学创新研究院，济南 250300
2.山东中医药大学第一临床医学院，济南 250014

收稿日期:2025-04-11 修回日期:2025-06-18 出版日期:2026-01-20 发布日期:2025-07-04
通讯作者: 杨雯晴，博士后，副教授，研究方向：中医药治疗心系疾病。E-mail: winnie0416q@163.com
作者简介:姜彤，硕士研究生，专业方向：中医药治疗心血管疾病。E-mail: jiangtong8900@163.com
基金资助:
山东省自然科学基金重点项目(ZR2020KH034);中国博士后科学基金项目(2023M732139)

Characterizing transcriptomic signatures and identifying hub differentially expressed genes in resistant hypertension

Tong Jiang¹(), Shijing Peng¹, Shanshan Wang¹, Yuqi Wang², Wenjie zhao¹, Wenqing Yang¹()

1. Innovation Research Institute，Shandong University of Traditional Chinese Medicine, Jinan 250300, China
2. First Clinical Medicine School, Shandong University of Traditional Chinese Medicine, Jinan 250014, China

Received:2025-04-11 Revised:2025-06-18 Published:2026-01-20 Online:2025-07-04
Supported by:
Natural Science Foundation of Shandong Province(ZR2020KH034);China Postdoctoral Science Foundation(2023M732139)

摘要/Abstract

摘要：

难治性高血压(resistant hypertension, RH)是高血压疾病谱中危险类型之一，发病机制复杂。为探寻该病相关核心差异基因，本研究对2022年收集自山东中医药大学附属医院及济南市第五人民医院的30份血液样本(10例高血压患者、10例RH患者、10名健康对照者)进行了转录组测序。利用DESeq2分析筛选出731个差异表达基因(differentially expressed genes, DEGs)，并通过加权基因共表达网络分析(weighted gene co-expression network analysis, WGCNA)鉴定出2个与RH显著相关的模块(含1,944个基因)。将模块基因与DEGs取交集获得229个关键DEGs。基因本体(Gene Ontology, GO)分析显示，这些关键DEGs显著富集于药物分解代谢过程、血红蛋白复合体、过氧化物酶活性等条目；京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes, KEGG)通路分析表明，这些DEGs与VEGF信号通路和线粒体自噬等通路相关。进一步构建蛋白质-蛋白质互作(protein-protein interaction, PPI)网络，并运用Cytoscape软件的cytohubba插件整合12种算法筛选核心基因(取各算法前20名基因交集)，初步确定GATA1、EPB42、ANK1、SNCA为核心差异基因。qRT-PCR验证结果证实GATA1与EPB42的表达变化与测序结果一致。该研究表明，RH的发生涉及多基因协同作用，核心基因(如GATA1、EPB42)及相关通路(如VEGF信号通路、线粒体自噬)的扰动可能在疾病进程中发挥重要作用，这为深入理解RH的病理机制提供了新线索。

关键词: 难治性高血压, 转录组学, 加权基因共表达网络分析

Abstract:

Resistant hypertension (RH) is one of the high-risk types within the spectrum of hypertensive disorders, characterized by a complex pathogenesis. To identify hub differentially expressed genes (DEGs) associated with this disease, this study performed transcriptome sequencing on 30 blood samples collected in 2022 from the Affiliated Hospital of Shandong University of Traditional Chinese Medicine and Jinan Fifth People's Hospital (comprising 10 hypertensive patients, 10 RH patients, and 10 healthy controls). Using DESeq2 analysis, 731 DEGs were initially screened. Subsequently, weighted gene co-expression network analysis (WGCNA) identified 2 modules significantly associated with RH (containing 1,944 genes). Taking the intersection of these module genes and the DEGs yielded 229 key DEGs. Gene Ontology (GO) enrichment analysis revealed that these key DEGs were significantly enriched in biological processes such as drug catabolic process, cellular components like hemoglobin complex, and molecular functions including peroxidase activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that these DEGs were associated with pathways such as the VEGF signaling pathway and mitophagy. A protein-protein interaction (PPI) network was further constructed. Using the cytohubba plugin in Cytoscape software, hub genes were identified by integrating the results from 12 algorithms (taking the intersection of the top 20 genes from each algorithm), preliminarily determining GATA1, EPB42, ANK1, and SNCA as the hub DEGs. Validation by qRT-PCR confirmed that the expression changes of GATA1 and EPB42 were consistent with the sequencing results. This study suggests that the development of RH involves the synergistic action of multiple genes, and perturbations in hub genes (GATA1, EPB42) and related pathways (VEGF signaling pathway, mitophagy) may play significant roles in the disease process. These findings provide new insights for a deeper understanding of the pathological mechanisms underlying RH.

Key words: resistant hypertension, transcriptomics, weighted gene co-expression network analysis (WGCNA)

姜彤, 彭世靖, 王姗姗, 王昱琪, 赵文杰, 杨雯晴. 转录组学测序解析难治性高血压基因表达特征及核心差异基因[J]. 遗传, 2026, 48(1): 76-86.

Tong Jiang, Shijing Peng, Shanshan Wang, Yuqi Wang, Wenjie zhao, Wenqing Yang. Characterizing transcriptomic signatures and identifying hub differentially expressed genes in resistant hypertension[J]. Hereditas(Beijing), 2026, 48(1): 76-86.

图/表 8

表1

表2

图1

图2

图3

图4

图5

图6

参考文献 33

[1]	Lamirault G, Artifoni M, Daniel M, Barber-Chamoux N. Resistant hypertension: novel insights. Curr Hypertens Rev, 2020, 16(1): 61-72. pmid: 31622203
[2]	Doroszko A, Janus A, Szahidewicz-Krupska E, Mazur G, Derkacz A. Resistant hypertension. Adv Clin Exp Med, 2016, 25(1): 173-183. pmid: 26935512
[3]	Daugherty SL, Powers JD, Magid DJ, Tavel HM, Masoudi FA, Margolis KL, O'Connor PJ, Selby JV, Ho PM. Incidence and prognosis of resistant hypertension in hypertensive patients. Circulation, 2012, 125(13): 1635-1642. pmid: 22379110
[4]	Carey RM, Calhoun DA, Bakris GL, Brook RD, Daugherty SL, Dennison-Himmelfarb CR, Egan BM, Flack JM, Gidding SS, Judd E, Lackland DT, Laffer CL, Newton-Cheh C, Smith SM, Taler SJ, Textor SC, Turan TN, White WB, American Heart Association Professional/ Public Education and Publications Committee of the Council on Hypertension, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, Council on Genomic and Precision Medicine, Council on Peripheral Vascular Disease, Council on Quality of Care and Outcomes Research, and Stroke Council. Resistant hypertension: detection,evaluation, and management: a scientific statement from the American Heart Association. Hypertension, 2018, 72(5): e53-e90. pmid: 30354828
[5]	Chen YH, Shyu YT, Lin SS. Characterization of candidate genes involved in halotolerance using high-throughput omics in the halotolerant bacterium Virgibacillus chiguensis. PLoS One, 2018, 13(8): e0201346. pmid: 30091990
[6]	Verdecchia P, Angeli F, Reboldi G. Does malaria cause hypertension? Circ Res, 2016, 119(1): 7-9. pmid: 27340264
[7]	Saraiva VB, de Souza Silva L, Ferreira-DaSilva CT, da Silva-Filho JL, Teixeira-Ferreira A, Perales J, Souza MC, Henriques MDG, Caruso-Neves C, de Sá Pinheiro AA. Impairment of the plasmodium falciparum erythrocytic cycle induced by angiotensin peptides. PLoS One, 2011, 6(2): e17174. pmid: 21364758
[8]	Maciel C, de Oliveira Junior VX, Fázio MA, Nacif- Pimenta R, Miranda A, Pimenta PFP, Capurro ML. Anti-Plasmodium activity of angiotensin II and related synthetic peptides. PLoS One, 2008, 3(9): e3296. pmid: 18820728
[9]	Zhao XX, Cui LM, Xiao Y, Mao Q, Aishanjiang M, Kong WZ, Liu YQ, Chen H, Hong F, Jia ZD, Wang M, Jiang PP, Guan MX. Hypertension-associated mitochondrial DNA 4401A>G mutation caused the aberrant processing of tRNAMet, all 8 tRNAs and ND6 mRNA in the light-strand transcript. Nucleic Acids Res, 2019, 47(19): 10340-10356. pmid: 31504769
[10]	Lu Y, Li S, Wu HF, Bian ZP, Xu JD, Gu CR, Chen XJ, Yang D. Beneficial effects of astragaloside IV against angiotensin II-induced mitochondrial dysfunction in rat vascular smooth muscle cells. Int J Mol Med, 2015, 36(5): 1223-1232. pmid: 26398547
[11]	Lin L, Shi AB. Endocytic recycling pathways and the regulatory mechanisms. Hereditas (Beijing), 2019, 41(6): 451-468.
	林珑, 史岸冰. 细胞内吞循环运输通路及其分子调控机制. 遗传, 2019, 41(6): 451-468.
[12]	Chen DX. Rab5a mediated AT₁R endocytosis underlines Liensinine mechanism of vascular function maintenance and hypertension therapy [Dissertation]. Fujian University of Traditional Chinese Medicine, 2023.
	陈达鑫. 基于Rab5a介导AT₁R内吞途径研究莲心碱保护血管功能防治高血压的作用机制[学位论文]. 福建中医药大学, 2023.
[13]	Ferrara N, Kerbel RS. Angiogenesis as a therapeutic target. Nature, 2005, 438(7070): 967-974. pmid: 16355214
[14]	Storkebaum E, de Almodovar CR, Meens M, Zacchigna S, Mazzone M, Vanhoutte G, Vinckier S, Miskiewicz K, Poesen K, Lambrechts D, Janssen GMJ, Fazzi GE, Verstreken P, Haigh J, Schiffers PM, Rohrer H, Van der Linden A, De Mey JGR, Carmeliet P. Impaired autonomic regulation of resistance arteries in mice with low vascular endothelial growth factor or upon vascular endothelial growth factor trap delivery. Circulation, 2010, 122(3): 273-281. pmid: 20606119
[15]	Benjamin EJ, Larson MG, Keyes MJ, Mitchell GF, Vasan RS, Keaney JF Jr, Lehman BT, Fan SX, Osypiuk E, Vita JA. Clinical correlates and heritability of flow-mediated dilation in the community: the Framingham Heart Study. Circulation, 2004, 109(5): 613-619. pmid: 14769683
[16]	Yu CN, Cantor AB, Yang HD, Browne C, Wells RA, Fujiwara Y, Orkin SH. Targeted deletion of a high-affinity GATA-binding site in the GATA-1 promoter leads to selective loss of the eosinophil lineage in vivo. J Exp Med, 2002, 195(11): 1387-1395. pmid: 12045237
[17]	Szalai G, LaRue AC, Watson DK. Molecular mechanisms of megakaryopoiesis. Cell Mol Life Sci, 2006, 63(21): 2460-2476. pmid: 16909203
[18]	Rothenberg ME, Hogan SP. The eosinophil. Annu Rev Immunol, 2006, 24(1): 147-174. pmid: 16551246
[19]	Kitamura Y, Oboki K, Ito A. Molecular mechanisms of mast cell development. Immunol Allergy Clin North Am, 2006, 26(3): 387-405. pmid: 16931285
[20]	Fan C, Ouyang P, Timur AA, He P, You SA, Hu Y, Ke T, Driscoll DJ, Chen QY, Wang QK. Novel roles of GATA1 in regulation of angiogenic factor AGGF1 and endothelial cell function. J Biol Chem, 2009, 284(35): 23331-23343. pmid: 19556247
[21]	Bai C, Wang JG, Li JX. Transcription factor GATA1 represses oxidized-low density lipoprotein-induced pyroptosis of human coronary artery endothelial cells. Clin Hemorheol Microcirc, 2023, 83(1): 81-92. pmid: 36120774
[22]	Yamashita M, Nakayama T. Progress in allergy signal research on mast cells: regulation of allergic airway inflammation through toll-like receptor 4-mediated modification of mast cell function. J Pharmacol Sci, 2008, 106(3): 332-335. pmid: 18360088
[23]	Buck I, Morceau F, Cristofanon S, Heintz C, Chateauvieux S, Reuter S, Dicato M, Diederich M. Tumor necrosis factor α inhibits erythroid differentiation in human erythropoietin- dependent cells involving p38 MAPK pathway, GATA-1 and FOG-1 downregulation and GATA-2 upregulation. Biochem Pharmacol, 2008, 76(10): 1229-1239. pmid: 18805401
[24]	Bibikova E, Youn MY, Danilova N, Ono-Uruga Y, Konto- Ghiorghi Y, Ochoa R, Narla A, Glader B, Lin S, Sakamoto KM. TNF-mediated inflammation represses GATA1 and activates p38 MAP kinase in RPS19-deficient hematopoietic progenitors. Blood, 2014, 124(25): 3791-3798. pmid: 25270909
[25]	Tyrkalska SD, Pérez-Oliva AB, Rodríguez-Ruiz L, Martínez-Morcillo FJ, Alcaraz-Pérez F, Martínez-Navarro FJ, Lachaud C, Ahmed N, Schroeder T, Pardo-Sánchez I, Candel S, López-Muñoz A, Choudhuri A, Rossmann MP, Zon LI, Cayuela ML, García-Moreno D, Mulero V. Inflammasome regulates hematopoiesis through cleavage of the master erythroid transcription factor GATA1. Immunity, 2019, 51(1): 50-63.e5. pmid: 31174991
[26]	Rodríguez-Ruiz L, Lozano-Gil JM, Lachaud C, Mesa- Del-Castillo P, Cayuela ML, García-Moreno D, Pérez-Oliva AB, Mulero V. Zebrafish models to study inflammasome-mediated regulation of hematopoiesis. Trends Immunol, 2020, 41(12): 1116-1127. pmid: 33162327
[27]	Cui YJ. Effect of levamlodipine besylate tablets as adjunctive therapy on serum Hcy, TNF-α, and IL-6 levels in elderly patients with resistant hypertension. Strait Pharmaceutical Journal, 2020, 32(05): 142-144.
	崔雨静. 苯磺酸左旋氨氯地平片辅助治疗老年难治性高血压的效果及对患者血清Hcy、TNF-α、IL-6水平的影响. 海峡药学, 2020, 32(05): 142-144
[28]	Zhang LF, Li Bo, Zhou MN. Correlation of inflammatory factor gene polymorphism with risk of stroke in essential hypertensive patients. Cardio-cerebrovascular Disease Prevention and Treatment, 2020, 20(4): 362-365.
	张立芳, 李博, 周美宁. 炎症因子基因多态性与原发性高血压患者发生脑卒中风险相关性. 心脑血管病防治, 2020, 20(4): 362-365.
[29]	Zhang YN. Screening and functional study of transcription factors regulating VEGF expression[Dissertation]. Chinese PLA Academy of Military Medical Sciences, 2016.
	张亚楠. 调控VEGF表达的转录因子的筛选及功能研究[学位论文]. 中国人民解放军军事医学科学院, 2016.
[30]	Kaczmarska M, Fornal M, Messerli FH, Korecki J, Grodzicki T, Burda K. Erythrocyte membrane properties in patients with essential hypertension. Cell Biochem Biophys, 2013, 67(3): 1089-1102. pmid: 23673613
[31]	Ma HT, Liu JC, Li ZL, Xiong HY, Zhang YL, Song YP, Lai JH. Expression profile analysis reveals hub genes that are associated with immune system dysregulation in primary myelofibrosis. Hematology, 2021, 26(1): 478-490. pmid: 34238135
[32]	Lu SL, Yadav AK, Qiao XH. Identification of potential miRNA-mRNA interaction network in bone marrow T cells of acquired aplastic anemia. Hematology, 2020, 25(1): 168-175. pmid: 32338587
[33]	Kim NH, Kim HS, Kim NG, Lee I, Choi HS, Li XY, Kang SE, Cha SY, Ryu JK, Na JM, Park C, Kim K, Lee S, Gumbiner BM, Yook JI, Weiss SJ. p53 and microRNA-34 are suppressors of canonical Wnt signaling. Sci Signal, 2011, 4(197): ra71. pmid: 22045851

编辑推荐

Metrics

www.chinagene.cn
备案号：京ICP备09063187号-4
总访问:,今日访问:,当前在线:

引物名称	引物序列(5′→3′)
GATA1-F	GTTAGCCACCTCATGCCTTTCC
GATA1-R	GAGCGGAGCCACCACAGTAG
EPB42-F	AGGCAGCAAGAAACAATGAGGAG
EPB42-R	CGGAAGTACAGGATGATGGTGAAG
ANK1-F	GCAGCGTCATTGGAGGAACAG
ANK1-R	GGCAGAGACATTGGTGGTGAAG
SNCA-F	AGTGGTGACGGGTGTGACAG
SNCA-R	TCCTTCTTCATTCTTGCCCAACTG

特征	N (n=10)	EH (n=10)	RH (n=10)
年龄(岁)	35.70±3.50	60.20±11.41^**	66±13.17^**
男性，n(%)	3(30)	5(50)	6(60)
收缩压(mmHg)	117.20±16.27	152.10±12.90^**	175.70±30.42^{** #}
舒张压(mmHg)	74.60±10.95	90.10±8.20^*	97.70±19.71^**
甘油三酯(mmol/L)	1.00±0.39	2.00±2.58	3.40±4.18
总胆固醇(mmol/L)	5.06±0.93	4.53±0.83	5.45±1.73
高密度脂蛋白胆固醇(mmol/L)	1.44±0.37	1.20±0.42	1.25±0.25
低密度脂蛋白胆固醇(mmol/L)	3.07±0.81	2.23±0.63	2.76±1.68

转录组学测序解析难治性高血压基因表达特征及核心差异基因

Characterizing transcriptomic signatures and identifying hub differentially expressed genes in resistant hypertension

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 8

参考文献 33

相关文章 4

编辑推荐

Metrics

[1]	时文睿, 渠鸿竹, 方向东. 痛风的多组学研究进展[J]. 遗传, 2023, 45(8): 643-657.
[2]	吕娇, 龚一富, 章丽, 胡媛, 王何瑜. 基于WGCNA发掘缺磷、红光和黄光处理下三角褐指藻岩藻黄素合成关键基因[J]. 遗传, 2023, 45(3): 237-249.
[3]	杨莹,陈宇晟,孙宝发,杨运桂. RNA甲基化修饰调控和规律[J]. 遗传, 2018, 40(11): 964-976.
[4]	赵艳李燕燕. 组学技术评价转基因农作物的非预期效应[J]. 遗传, 2013, 35(12): 1360-1367.