冠心病血瘀证遗传相关的差异基因筛选及其功能路径分析  

The Screening and the Functional Pathway Analysis of Differential Genes Correlated with Coronary Heart Disease of Blood Stasis Syndrome

作　　者：袁肇凯[1] 王丽萍[1] 黄献平[2] 李杰[2] 王萍[1] 喻松仁[1] 简维雄[2] 孙贵香[2] 刘群良[2] 郑景辉[1] 

机构地区：[1]湖南中医药大学中医诊断学国家重点学科,长沙410007 [2]湖南中医药大学病理生理国家中医药管理局三级科研实验室,湖南中医药大学中医病证湖南省重点实验室,长沙410007

出　　处：《中国中西医结合杂志》2012年第10期1313-1318,共6页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：国家自然科学基金资助项目(No.30973717);国家自然科学基金青年基金资助项目(No.81001518);湖南省研究生创新基金资助项目(No.cx2010B339)

摘　　要：目的探讨冠心病(coronary heart disease,CHD)血瘀证遗传相关的差异基因功能及目标通路。方法以家系CHD血瘀证者(A组)及家系CHD非血瘀证者(B组)、家系非CHD血瘀证者(C组)、家系健康人(D组)、非家系CHD血瘀证者(E组)、非家系健康人(F组)为研究对象,应用基因芯片技术比较A组与B、C、D、E组,以及D组与F组的差异基因表达谱;通过基因本体论(geneontology,GO)分析阐释差异基因的分子功能;通过BioCarta及KEGG网站寻找差异基因所在通路,应用超几何分布统计学方法分析筛选出有意义的目标通路,并用实时荧光定量RT-PCR对差异基因进行验证。结果 (1)通过对基因芯片数据的筛选(差异倍数≥3),发现家系CHD血瘀证差异基因表达主要涉及趋化因子、白介素细胞因子、补体系统、基质金属蛋白酶系、成纤维细胞生长因子、内皮细胞黏附因子等。(2)通过相关差异基因(P<0.05)GO分析,找到与CHD血瘀证相关的差异基因的分子功能。(3)经过BioCarta及KEGG通路分析,发现家系CHD血瘀证与遗传相关的差异基因中差异有统计学意义(P<0.05)的目标通路主要涉及到炎症、斑块形成、内皮损伤等方面。经实时荧光定量RT-PCR反应验证了基因芯片准确可靠。结论 CHD血瘀证遗传相关的差异基因与炎症、斑块形成及血管内皮损伤密切相关。Objective To explore the function and target pathway of the correlated differential gene of cor- onary heart disease （CHD） of blood stasis syndrome （BSS）. Methods Patients of the genealogical CHD of BSS （Group A） and the genealogical CHD of non-BSS （Group B）, the genealogical non-CHD of BSS （Group C）, the genealogical healthy subjects （Group D）, the non-genealogical CHD of BSS （Group E）, the non-gene- alogical healthy subjects （Group F） were recruited in this study. The defferential gene expression spectrums were studied using gene chip technique. The molecular functions of differential genes were analyzed and illustra- ted by Gene Ontology （GO） analysis. The differential gene pathways were found out at BioCarta and KEGG. The meaningful target pathways were screened by hypergeometric distribution statistical method. The differential genes were verified using Real-time fluorescent quantitative PCR. Results （1） By screening the gene chip data （with FC I〉3）, we found the expressions of differential genes of CHD of BSS were mainly involved in chemokine, interleukin cytokine, alexin system, matrix metal proteinase system, fibroblastic growth factor, endothelial cell ad- hesion molecule, and so on. （2） By GO analysis of related differential genes （P〈0.05）, we found the molecu- lar functions of differential genes associated with CHD BSS. （3） By BioCarta and KEGG pathway analysis, we found the target pathways of the hereditary correlated differential genes of CHD BSS with significance were mainly involved in inflammation, plaque formation, endothelial injury, and so on. The results of Real-time fluorescent quantitative RT-PCR proved the accuracy of the gene chip. Conclusion The hereditary correlated differential genes of CHD BSS were closely associated with inflammation, plaque formation, and endothelial injury.

关 键 词：冠心病 血瘀证 遗传 家系 差异基因 

分 类 号：R259[医药卫生—中西医结合]