早发冠心病血瘀证DNA羟甲基化相关差异基因研究

Study on the DNA hydroxymethylation related difference genes in premature coronary heart disease with blood stasis syndrome

目的 探讨早发冠心病(premature coronary heart disease,PCHD)血瘀证DNA羟甲基化相关差异基因表达,以期寻找PCHD血瘀证诊断和治疗的新靶点。方法 病例来自湖南中医药大学第二附属医院PCHD患者,分为PCHD血瘀证组(A组)和PCHD非血瘀证组(B组),各6例,采用DNA羟甲基化免疫共沉淀芯片技术分析两组的相关羟甲基化差异基因表达情况,并对其进行聚类分析、KEGG通路富集分析及GO功能富集分析。结果 A组与B组相比,高CpG密度启动子差异羟甲基化基因数目343个,低CpG密度启动子差异羟甲基化基因数目144个,通路富集分析得出PCHD血瘀证羟甲基化差异基因主要与细胞周期、心肌能量代谢、炎症、内皮损伤有关,GO功能富集分析得出PCHD血瘀证生物学功能多与细胞发育和分化、蛋白酶活性、细胞内结构等有关。A组的CDKN1B、HDAC2、MDM2羟甲基化表达程度均较高。结论 PCHD血瘀证差异基因羟甲基化表达程度较高,这些差异基因主要与转录调控心肌细胞周期有关,可能影响心肌细胞周期阻滞、凋亡、衰老等,导致疾病的发生发展,为PCHD血瘀证诊断和治疗提供一定的参考。

Objective To explore the differential expression of DNA hydroxylmethylation related genes in premature coronary heart disease(PCHD) with blood stasis syndrome,in order to find a new target for diagnosis and treatment of PCHD with blood stasis syndrome.Methods The patients were from PCHD patients in The Second Affiliated Hospital of Hunan University of Chinese Medicine.They were divided into PCHD with blood stasis syndrome group(group A) and PCHD with non-blood stasis syndrome group(group B),with 6 patients in each group.DNA hydroxymethylated immunoprecipitation chip technique was used to analyze the differential gene expression of related hydroxymethylation between the two groups.Cluster analysis,KEGG pathway enrichment analysis and GO function enrichment analysis were performed.Results Compared with group B,group A had343 differential hydroxymethylation genes with high CpG density promoter and 144 differential hydroxymethylation genes with low CpG density promoter.Pathway enrichment analysis showed that the differential genes of hydroxymethylation in PCHD with blood stasis syndrome were mainly related to cell cycle,myocardial energy metabolism,inflammation and endothelial injury.Go function enrichment analysis showed that the biological functions of PCHD with blood stasis syndrome were mostly related to cell development and differentiation,protease activity,intracellular structure and so on.The degree of hydroxymethylation of CDKN1B,HDAC2,MDM2 in group A was higher than that in group B.Conclusion The expression degree of hydroxymethylation of differential genes in PCHD with blood stasis syndrome is higher.These differential genes are mainly related to transcriptional regulation of myocardial cell cycle,which may affect cardiomyocyte cycle arrest,apoptosis,senescence and so on,leading to the occurrence and development of the disease,which provides a reference for the diagnosis and treatment of PCHD with blood stasis syndrome.