Investigation of the underlying genes and mechanism of familial hypercholesterolemia through bioinformatics analysis.
BACKGROUND
Familial hypercholesterolemia (FH) is one of the commonest inherited metabolic disorders. Abnormally high level of low-density lipoprotein cholesterol (LDL-C) in blood leads to premature atherosclerosis onset and a high risk of cardiovascular disease (CVD). However, the specific mechanisms of the progression process are still unclear. Our study aimed to investigate the potential differently expressed genes (DEGs) and mechanism of FH using various bioinformatic tools.


METHODS
GSE13985 and GSE6054 were downloaded from the Gene Expression Omnibus (GEO) database for bioinformatic analysis in this study. First, limma package of R was used to identify DEGs between blood samples of patients with FH and those from healthy individuals. Then, the functional annotation of DEGs was carried out by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and Gene Ontology (GO) analysis. Based on Search Tool for the Retrieval of Interacting Genes (STRING) tool, we constructed the Protein-Protein Interactions (PPIs) network among DEGs and mined the core genes as well.


RESULTS
A total of 102 communal DEGs (49 up-regulated and 53 down-regulated) are identified in FH samples compared with control samples. The functional changes of DEGs are mainly associated with the focal adhere and glucagon signaling pathway. Ten genes (ITGAL, TLN1, POLR2A, CD69, GZMA, VASP, HNRNPUL1, SF1, SRRM2, ITGAV) were identified as core genes. Bioinformatic analysis showed that the core genes are mainly enriched in numerous processes related to cell adhesion, integrin-mediated signaling pathway and cell-matrix adhesion. In the transcription factor (TF) target regulating network, 219 nodes were detected, including 214 DEGs and 5 TFs (SP1, EGR3, CREB, SEF1, HOX13). In conclusion, the DEGs and hub genes identified in this study may help us understand the potential etiology of the occurrence and development of AS.


CONCLUSION
Up-regulated ITGAL, TLN1, POLR2A, VASP, HNRNPUL1, SF1, SRRM2, and down-regulated CD69, GZMA and ITGAV performed important promotional effects for the formation of atherosclerotic plaques those suffering from FH. Moreover, SP1, EGR3, CREB, SEF1 and HOX13 were the potential transcription factors for DEGs and could serve as underlying targets for AS rupture prevention. These findings provide a theoretical basis for us to understand the potential etiology of the occurrence and development of AS in FH patients and we may be able to find potential diagnostic and therapeutic targets.
['Wang|Dinghui|D|', 'Liu|Bin|B|', 'Xiong|Tianhua|T|', 'Yu|Wenlong|W|', 'She|Qiang|Q|0000-0001-5049-1264']
D050197:Atherosclerosis D016022:Case-Control Studies D008078:Cholesterol, LDL D019295:Computational Biology D030541:Databases, Genetic D018450:Disease Progression D005786:Gene Expression Regulation D053263:Gene Regulatory Networks D056726:Genetic Association Studies D020022:Genetic Predisposition to Disease D006801:Humans D006938:Hyperlipoproteinemia Type II D010641:Phenotype D060066:Protein Interaction Maps D015398:Signal Transduction
Familial hypercholesterolemia Bioinformatics analysis LDL-C Atherosclerosis ITGAL TLN1