Dysfunctional co-expression network analysis of familial hypercholesterolemia

Abstract

Familial hypercholesterolemia (FH) is an inherited disorder of blood lipid metabolism characterized by high serum low-density lipoprotein cholesterol levels and premature coronary artery disease. In this study, we used a system biology approach to identify co-expressed gene pairs that were potentially involved in the progression of FH and constructed a conserved co-expression network using these genes. A total of 4232 co-expressed relationships were identified and we verified the significance by random permutation. FH patients showed differences in lipoprotein and cholesterol metabolism in circulating monocytes and lymphocytes compared to healthy controls. We hope our study could aid in understanding of FH and could provide the basis for FH biomarker identification.

Network Medicine Approach in Prevention and Personalized Treatment of Dyslipidemias

“…2). We report the most current studies applying integrated network‐oriented analysis to identify putative risk biomarkers and drug targets (Table 1) (Adiels et al, 2018; Chen et al, 2014; Miao et al, 2019; Wang and Loscalzo, 2018; Yao et al, 2015; Ye et al, 2013).…”

“…By using available microarray datasets performed on T cells and monocytes isolated from FH patients, a co‐expression network of differentially expressed (DE) transcripts was built. The analysis revealed a set of perturbed gene pairs in cholesterol lipoprotein metabolism (Ye et al, 2013). Remarkably, through a GO analysis, chronic myeloid leukemia, neurotrophin signaling pathway, and SNARE protein interactions in vesicular transport have been suggested, as key deregulated signaling pathways in FH (Ye et al, 2013).…”

“…The analysis revealed a set of perturbed gene pairs in cholesterol lipoprotein metabolism (Ye et al, 2013). Remarkably, through a GO analysis, chronic myeloid leukemia, neurotrophin signaling pathway, and SNARE protein interactions in vesicular transport have been suggested, as key deregulated signaling pathways in FH (Ye et al, 2013). Another microarray platform performed on circulating monocytes traced a map of 443 DE transcripts able to distinguish FH patients from healthy controls (Chen et al, 2014).…”

Network Medicine: A Clinical Approach for Precision Medicine and Personalized Therapy in Coronary Heart Disease

“…Similarly, Gallium-68, labelled DOTATATE, targets the somatostatin receptor subtype 2 (SSTR2) found on the surface of macrophages. Pre-clinical studies have confirmed 68 Ga-DOTATATE's superiority over FDG in terms of macrophage specificity in atherosclerotic inflammation and in discriminating between unstable and stable coronary plaques 54) . 18 F-fluorocholine ( 18 F-FCH), a PET tracer with potential antiinflammatory affinity, shows a strong association between large vessel uptake and atherosclerotic changes in the arterial walls, with an apparent inverse relationship with calcification 54) .…”

“…2), 18 of which were associated with the cardiovascular system, confirmed the key functional role of seed connectors functional pathways of leukocyte subsets from FH patients and healthy individuals. A total of 4,232 coexpressed relationships were identified in patients showing dysregulation in lipoprotein and cholesterol metabolism as well as neurotrophin signaling (SNARE proteins), MAPK pathways, and endocytosis processes, suggesting an altered transport of low-density lipoprotein receptor (LDLR) across membrane 68) .…”