全基因组芯片结合通路分析筛选心力衰竭患者心肌细胞差异基因

Identification of differentially expressed genes in myocardium of patients with heart failure by human whole genomic oligonucleotide microarray-assisted pathways analysis

目的利用人全基因组芯片分析心力衰竭（心衰）患者与正常人心肌细胞差异表达基因，结合已知基因功能分类着重对细胞信号通路进行分析。方法应用华联公司人全基因组芯片，检测4例心衰患者及4例脑死亡的正常人心肌细胞的基因表达谱，并以实时荧光定量PCR技术对基因芯片检测结果进行验证。将心衰差异表达量≥1.2倍或≤-1.2倍的基因经BioCarta通路和KEGG通路进行信号通路分析。结果4例心衰心肌标本与正常对照比较，表达量变化1.2倍以上的基因有2806条；变化2倍以上的有399条基因。经BioCarta通路分析，心衰时涉及11条通路蛋白。经KEGG通路分析，涉及16条通路。结论心衰时心肌细胞中有大量的基因呈现差异表达，并激活了多条促进细胞凋亡通路及涉及转录调控的通路。运用基因芯片和生物学通路相结合的方法，分析基因表达谱能准确而且有的放矢地研究与心衰病理生理的相关基因。

Objective To identify the differentially expressed gene profiles in myocardium of patients with heart failure using human whole genomic oligonucleotide microarray-assisted pathway analysis. Methods Phalanx whole genomic nhgonucleotide microarrays were used to detect the gene expression profiles of myocardium in four patients died of heart failure and 4 brain died patients without heart diseases. The microarray findings were confirmed by real-time quantitative reverse transcriptase-polymerase chain reaction. The genes with a threshold of 1.2 times fold-change were selected and BioCarta Pathway and KEGG （ Kyoto Encyclopaedia of Genes and Genomes） pathway databases were used to identify functionally related gene pathways. Results A total of 2806 genes with differentially expression were detected between the failing and non-failing heart samples, expression changes of 399 genes were more than 2-folds. Eleven pathways were identified by BioCarta pathway database and sixteen pathways were identified by KEGG PATHWAY Database. Conclusion Genomic microarray-assisted pathway analysis could help to identify gene expression profiles in failing heart.