儿童肥胖症相关基因的生物信息学分析
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摘要
目的筛选儿童肥胖症相关基因,探索儿童肥胖症的发病机制。方法从基因表达公共数据库(GEO)下载儿童肥胖症基因表达谱数据集GSE9624,采用BRB-Array Tools软件包筛选差异表达基因(DEGs),并对差异基因进行GO功能分析、KEGG通路富集分析和pathway相互作用网络分析。结果共筛选出564个DEGs,其中上调基因333个,下调基因231个。GO富集分析发现DEGs主要参与代谢、细胞因子反应、信号转导、血液凝固等生物学过程,发挥的分子功能包括蛋白结合、蛋白二聚化、离子结合、RNA结合和ATP结合等。KEGG通路分析发现DEGs显著富集的pathway有代谢通路、MAPK信号通路、吞噬体、内质网蛋白加工、T细胞受体通路等。结论儿童肥胖症患者代谢通路和信号转导通路的相关基因表达水平发生了改变,为进一步阐明儿童肥胖症的分子机制和靶向治疗提供了基础。
Objective To screen the genes involved in childhood obesity and explore the pathogenesis mechanism of childhood obesity.Methods The dataset GSE9624 containing the gene expression profiles of obese children was downloaded from the Gene Expression Omnibus(GEO)database.The differentially expressed genes(DEGs)were screened using BRB.Array Tools software,then the GO function,KEGG enrichment analysis,and pathway relation network analyses were performed based on these differential genes.Results Totally,564 differential genes were identified,of which333 genes were upregulated and 231 genes were downregulated.GO en richment analysis showed that DEGs mainly participated in biologicaI process of metabolic process,response to cytokine stimulus,signal transduction,blood coagulation,and performed the molecular functions of protein binding,protein homodimerization activity,ion binding,RNA binding,and ATP binding.KEGG enrichment analysis suggested that DEGs were involved in metabolic pathways,MAPK signaling pathway,phagosome,protein processing in endoplasmic reticulum and T cell receptor signaling pathway.Conclusion Genes involved in metabolic and signalling pathways are altered in obese children,which provides the foundation for further understanding the molecular pathogenesis of childhood obesity and developing treatments for this disorder.
Objective To screen the genes involved in childhood obesity and explore the pathogenesis mechanism of childhood obesity.Methods The dataset GSE9624 containing the gene expression profiles of obese children was downloaded from the Gene Expression Omnibus(GEO)database.The differentially expressed genes(DEGs)were screened using BRB.Array Tools software,then the GO function,KEGG enrichment analysis,and pathway relation network analyses were performed based on these differential genes.Results Totally,564 differential genes were identified,of which333 genes were upregulated and 231 genes were downregulated.GO en richment analysis showed that DEGs mainly participated in biologicaI process of metabolic process,response to cytokine stimulus,signal transduction,blood coagulation,and performed the molecular functions of protein binding,protein homodimerization activity,ion binding,RNA binding,and ATP binding.KEGG enrichment analysis suggested that DEGs were involved in metabolic pathways,MAPK signaling pathway,phagosome,protein processing in endoplasmic reticulum and T cell receptor signaling pathway.Conclusion Genes involved in metabolic and signalling pathways are altered in obese children,which provides the foundation for further understanding the molecular pathogenesis of childhood obesity and developing treatments for this disorder.
引文
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[2]Hossain P,Kawar B,El Nahas M.Obesity and diabetes in the developing world--agrowing challenge[J].N Engl J Med,2007,356(3):213-215.
[3]Xu S,Xue Y.Pediatric obesity:Causes,symptoms,prevention and treatment[J].Exp Ther Med,2016,11(1):15-20.
[4]Nielsen LA,Nielsen TR,Holm JC.The Impact of Familial Predisposition to Obesity and Cardiovascular Disease on Childhood Obesity[J].Obes Facts,2015,8(5):319-328.
[5]Hill AP,Zuckerman KE,Fombonne E.Obesity and Autism[J].Pediatrics,2015,136(6):1051-1061.
[6]Dong Z,Chen Y.Transcriptomics:advances and approaches[J].Sci China Life Sci,2013,56(10):960-967.
[7]Kiyama R,Zhu Y.DNA microarray-based gene expression profiling of estrogenic chemicals[J].Cell Mol Life Sci,2014,71(11):2065-2082.
[8]Tusher VG,Tibshirani R,Chu G.Significance analysis of microarrays applied to the ionizing radiation response[J].Proc Natl Acad Sci USA,2001,98(9):5116-5121.
[9]Hu JX,Zhao H,Zhou HH.False Discovery Rate Control With Groups[J].J Am Stat Assoc,2010,105(491):1215-1227.
[10]Kanehisa M,Goto S,Kawashima S,et al.The KEGG resource for deciphering the genome[J].Nucleic Acids Res,2004,32(Database issue):277-280.
[11]Xie C,Mao X,Huang J,et al.KOBAS 2.0:a web server for annotation and identification of enriched pathways and diseases[J].Nucleic Acids Res,2011,39(Web Server issue):W316-322.
[12]Zhuang Q,Mao W,Xu P,et al.Identification of Differential Genes Expression Profiles and Pathways of Bone Marrow Mesenchymal Stem Cells of Adolescent Idiopathic Scoliosis Patients by Microarray and Integrated Gene Network Analysis[J].Spine,2016,41(10):840-855.
[13]李显兰.儿童、青少年肥胖症的流行现状及病因探讨[J].重庆医学,2013,42(2):226-228.
[14]张晓阳,陈国敏.肥胖儿童血液流变学检测的临床意义[J].实用心脑肺血管病杂志,2005,13(3):142-144.
[15]Ren D,Li M,Duan C,et al.Identification of SH2-B as a key regulator of leptin sensitivity,energy balance,and body weight in mice[J].Cell Metab,2005,2(2):95-104.
[16]Duan C,Li M,Rui L.SH2-B promotes insulin receptor substrate 1(IRS1)-and IRS2-mediated activation of the phosphatidylinositol 3-kinase pathway in response to leptin[J].J Biol Chem,2004,279(42):43684-43691.
[17]杨曦,沈沭彤,郭军.肥胖症易感基因——FTO的研究进展[J].生命科学,2011,23(05):459-464.
[18]Beckers S,Zegers D,de Freitas F,et al.Identification and functional characterization of novel mutations in the melanocortin-4receptor[J].Obes Facts,2010,3(5):304-311.
[19]洪楠超,赵越,刘晓,等.单基因肥胖症的遗传机制和治疗[J].中华老年多器官疾病杂志,2014,13(2):157-160.
[20]Pal A,Barber TM,Van de Bunt M,et al.PTEN mutations as a cause of constitutive insulin sensitivity and obesity[J].N Engl J Med,2012,367(11):1002-1011.