Transcriptome and miRNA network analysis of familial hypercholesterolemia.
[wiskott-aldrich syndrome]
Familial hypercholesterolemia (FH) is a genetic disorder characterized by a high serum concentration of low-density lipoprotein (LDL) cholesterol. The high LDL cholesterol level leads to an excess deposition of cholesterol in the arterial walls and accelerated atherosclerosis, thereby increasing the risk of premature coronary heart disease. In the present study, we used a DNA microarray approach to identify gene expression profiles that distinguish patients with FH from healthy control subjects. Furthermore, transcription factors (TFs), microRNAs (miRNAs), target genes and pathways were analyzed to explore the potential transcriptional interactions occurring in FH. Publicly available microarray and regulation data were used to construct a regulatory network to identify additional genes related to FH and their interactions. The results revealed that specificity protein 1 (SP1), signal transducer and activator of transcription 1 (STAT1) and spleen focus forming virus (SFFV) proviral integration oncogene spi1 (SPI1) play a central role in the FH regulatory network. In addition, the TF, upstream transcription factor 2, c-fos interacting (USF2) and the gene, Wiskott-Aldrich syndrome (WAS), were identified to be associated with FH, although no reports for these proteins exist in the literature. Overall, transcriptional network analysis proved to be effective approach to identify novel targets for FH therapy.
