Luo Xiaoli, Yu Changqing, Fu Chunjiang, Shi Weibin, Wang Xukai, Zeng Chunyu, Wang Hongyong
Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing Institute of Cardiology, Chongqing 400042, P.R. China.
Mol Med Rep. 2015 Jun;11(6):4032-8. doi: 10.3892/mmr.2015.3263. Epub 2015 Jan 27.
The aim of the present study was to screen the differentially expressed genes (DEGs) associated with familial combined hyperlipidemia (FCHL) and examine the changing patterns. The transcription profile of GSE18965 was obtained from the NCBI Gene Expression Omnibus database, including 12 FCHL samples and 12 control specimens. The DEGs were identified using a linear models for microarray data package in the R programming language. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was also performed. Protein‑protein interaction (PPI) networks of the DEGs were constructed using the EnrichNet online tool. In addition, cluster analysis of the genes in networks was performed using ClusterONE. A total of 879 DEGs were screened, including 394 upregulated and 485 downregulated genes. Enrichment analysis identified four important KEGG pathways associated with FCHL: One carbon pool by folate, α‑linolenic acid metabolism, asthma and the glycosphingolipid biosynthesis‑globo series. GO annotation identified 12 enriched biological processes, including one associated with hematopoiesis and four associated with bone cell differentiation. This identification was in accordance with clinical data and experiments into hyperlipidemia and bone lesions. Based on PPI networks, these DEGs had a close association with immune responses, hormone responses and cytokine‑cytokine receptors. In conclusion, these DEGs may be used as specific therapeutic molecular targets in the treatment of FCHL. The present findings may provide the basis for understanding the pathogenesis of FCHL in future studies. However, further experiments are required to confirm these results.
本研究的目的是筛选与家族性混合型高脂血症（FCHL）相关的差异表达基因（DEGs），并研究其变化模式。从NCBI基因表达综合数据库中获取GSE18965的转录谱，其中包括12个FCHL样本和12个对照样本。使用R编程语言中的微阵列数据包线性模型来识别DEGs。还进行了基因本体论（GO）功能和京都基因与基因组百科全书（KEGG）通路富集分析。使用EnrichNet在线工具构建DEGs的蛋白质-蛋白质相互作用（PPI）网络。此外，使用ClusterONE对网络中的基因进行聚类分析。共筛选出879个DEGs，包括394个上调基因和485个下调基因。富集分析确定了与FCHL相关的四个重要KEGG通路：叶酸一碳池、α-亚麻酸代谢、哮喘和糖鞘脂生物合成-球系列。GO注释确定了12个富集的生物学过程，包括一个与造血相关的过程和四个与骨细胞分化相关的过程。这一鉴定与高脂血症和骨病变的临床数据及实验结果一致。基于PPI网络，这些DEGs与免疫反应、激素反应和细胞因子-细胞因子受体密切相关。总之，这些DEGs可作为治疗FCHL的特异性治疗分子靶点。本研究结果可为未来研究中理解FCHL的发病机制提供依据。然而，需要进一步的实验来证实这些结果。
