首页|高血压脑出血血管病变关键基因初步筛选

高血压脑出血血管病变关键基因初步筛选

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目的 筛选出高血压脑出血(hypertensive intracerebral hemorrhage,HICH)血管病变的关键基因,为干预HICH提供新的候选靶点.方法 从小鼠基因组信息数据库(Mouse Genome Informatics,MGI)中筛选得到149个有脑出血表型的基因,建立基因集MGI-149;构建HICH动物模型并对脑血管进行转录组测序分析,建立HICH脑血管差异表达基因集HICH-DEG.通过基因本体(gene ontology,GO)富集分析和蛋白质-蛋白质相互作用(protein-protein interaction,PPI)分析,构建GO/PPI评分系统.结合基因重要性分析,在上述两个基因集的交集基因以及HICH-DEG基因集中筛选HICH血管病变关键基因,并用GeneMANIA对初筛基因进行分析和预测,以了解初筛基因参与HICH血管病变的潜在生物学功能和通路.结果 通过CeneMANIA预测及基于预测进行的富集分析,结合文献调研,舍弃缺少预测结果和文献支持的基因Zfp697、Gm11738,最终获得Ctnnb1、Kdr、Syk、Tnf和Abca1五个基因作为初筛关键基因.结论 本研究初步筛选出基因Ctnnb1、Kdr、Syk、Tnf、Abca1,它们可能在HICH血管病变中发挥关键作用,并有可能成为HICH临床前干预的重要靶标.
Preliminary Screening of the Key Genes of Vasculopathy in Hypertensive Intracerebral Hemorrhage
Objective To screen out the key genes of hypertensive intracerebral hemorrhage(HICH)and provide new candidate targets for the preclinical intervention of HICH.Methods The Mouse Genome Informatics(MGI)intracerebral hemorrhage phenotype gene set(MGI-149)was established by using the MGI database.The cerebrovascular differential expression gene set of hypertensive intracerebral hemorrhage(HICH-DEG)was established by building the HICH animal models and conducting an analysis of cerebrovascular transcriptome sequencing.The gene ontology(GO)/protein-protein interaction(PPI)scoring system was constructed through GO enrichment analysis and PPI analysis.The GIC scoring system was also constructed by gene importance analysis.We used both scoring systems to screen out the key genes from the overlapping genes of the two gene sets and the HICH-DEG gene set respectively.GeneMANIA was employed to analyze and predict the underlying interaction targets of these primary screened genes,followed by enrichment analysis of them to understand which potential biological functions or pathways may be involved in the pathogenesis of HICH vasculopathy.Moreover,we searched articles related to the screened genes to inspect and verify their relationships with HICH.Results Through GeneMANIA prediction,enrichment analysis based on prediction,and literature research,we discarded genes Zfp697 and Gm11738 that lacked prediction results and literature support,and ultimately obtained five genes,Ctnnb1,Kdr,Syk,Tnf,and Abca1,as the key genes for initial screening.Conclusion Genes Ctnnb1,Kdr,Syk,Tnf,and Abca1 are screened as key genes.They may play important roles in the vascular pathogenesis of HICH and become important targets of preclinical intervention.

Gene screeningCerebrovascularHypertensive intracerebral hemorrhageEnrichment analysisProtein-protein interaction

吴承益、宋莉、肖宁、刘晶、孙莹莹、陈敬洲

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郑州大学华中阜外医院 国家心血管病中心华中分中心 国家卫生健康委心血管再生医学重点实验室,郑州 450046

中国医学科学院 北京协和医学院 国家心血管病中心 阜外医院 心血管疾病国家重点实验室,北京 100037

中国医学科学院 北京协和医学院 国家心血管病中心 阜外医院健康生活方式医学中心,北京 100037

基因筛选 脑血管 高血压脑出血 富集分析 蛋白质-蛋白质相互作用

国家自然科学基金

82130013

2024

中国分子心脏病学杂志
中国医学科学院,中国协和医学院

中国分子心脏病学杂志

CSTPCD
影响因子:0.426
ISSN:1671-6272
年,卷(期):2024.24(2)
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