TABLE 4.

Description and potential functions of 10 genes selected from the 55 intersecting genes expressed in both FH and FH-CHD but not in N, H, and CHD groups.

Gene ID	Description	Function
MAPK14	Mitogen-activated protein kinase 14; p38 MAPK	Its activation promotes cardiomyocyte hypertrophy (Zechner et al., 1997; Liang and Molkentin, 2003), promotes myocyte apoptosis (Sharov et al., 2003) via downstream targets STAT1, CHOP, FAK, SMAD, cytochrome c, NF-κB, PTEN, and p53 (Fiordaliso et al., 2001; Ghosh et al., 2009), and regulate cardiomyocyte cytokinesis and promote cell cycle exit (Engel et al., 2006).
TRPM2	Transient receptor potential cation channel subfamily M member 2	The encoded protein is activated by oxidative stress and confers susceptibility to cell death (Maglott et al., 2011). Ca2+ entry via TRMP2 is necessary for proper cardiac function through modulation of mitochondrial oxidative signals, especially after I/R and reducing reactive oxygen species levels. TRPM2 is also protective of doxorubicin cardiomyopathy (Miller et al., 2014; Hoffman et al., 2015).
STARD8	StAR related lipid transfer domain containing 8; Rho-GTPase-activating-protein domain (RhoGAP)	This gene encodes a member of a subfamily of Rho GTPase activating proteins that contain a steroidogenic acute regulatory protein related lipid transfer domain. The encoded protein localizes to focal adhesions and may be involved in regulating cell morphology. START proteins are involved in several different biological processes: lipid transfer between cellular compartments; lipid metabolism, which involves START proteins that contain thioesterase catalytic activities; and signal transduction, which involves the RhoGAP START proteins (Alpy and Tomasetto, 2005).
PDLIM5	PDZ and LIM domain 5	PDLIM5 encodes several splice variants, whose expression is tissue specific and temporally regulated (Zheng et al., 2010). Alternative splicing plays an important role in heart development and in the development of cardiopathies (Weeland et al., 2015). Polymorphisms in PDLIM3 (rs4861669, rs4862543) and PDLIM5 (rs1056772) were significantly associated with idiopathic dilated cardiomyopathy (IDCM) in Chinese Han patients (Wang et al., 2019)
BCL3	BCL3 transcription coactivator	BCL3 gene expression is induced via NF-κB and play role in cell proliferation regulation (Ohno et al., 1990; Wulczyn et al., 1992). Down regulated expression of BCL3 gene affect their transcription regulatory networks, which subsequently alter a number of biological processes in human ischemia cardiomyopathy (Herrer et al., 2015).
BLOC1S5	Biogenesis of lysosomal organelles complex 1 subunit 5	Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules. Dense granules are important in platelet aggregation and play role in thrombus formation (Ambrosio et al., 2012).
GBA	Glucosylceramidase beta	Glucosylceramidase that catalyzes the hydrolysis of glucosylceramide/GlcCer into free ceramide and glucose within the lysosomal compartment. Thereby, GBA plays a central role in the degradation of complex lipids and the turnover of cellular membranes (Rijnboutt et al., 1991). Under specific conditions, GBA may alternatively catalyze the reverse reaction, transferring glucose from cholesteryl-beta-D-glucoside to ceramide, finally, may also hydrolyze cholesteryl-beta-D-glucoside to produce D-glucose and cholesterol (Akiyama et al., 2013; Marques et al., 2016). Alterations in the level of glucosylceramide are noted in cells and tissues in response to cardiovascular disease, diabetes, skin disorders and cancer. Reducing synthesis of glycosphingolipids with pathological effects could be a new approach for preventing cardiac hypertrophy. Overall, upregulation of glucosylceramide offers cellular protection and primes certain cells for proliferation (Messner and Cabot, 2010).
RBMS1	RNA binding motif single stranded interacting protein 1	This gene encodes a member of a small family of proteins, which bind single stranded DNA/RNA. These proteins are characterized by the presence of two sets of ribonucleoprotein consensus sequence (RNP-CS) that contain conserved motifs, RNP1 and RNP2, originally described in RNA binding proteins, and required for DNA binding. These proteins have been implicated in such diverse functions as DNA replication, gene transcription, cell cycle progression and apoptosis (Maglott et al., 2011). RBMS1 interact with polymerase (DNA directed), alpha 1 (Niki et al., 2000).
CD14	Cluster of differentiation 14 molecule	CD14 is expressed mainly by macrophages in innate immunity (Simmons et al., 1989). CD14 acts as co-receptor for Toll like receptor (TLR) 4 and MD-Z in response to lipopolysaccharide (LPS) (Kitchens et al., 2000). Increase in proinflammatory monocyte (CD14+CD16+) is an independent risk factor for CAD and plaque process (Schlitt et al., 2004). Monocyte (CD14++CD16+) and neutrophil may be involved in small to large vessel vasculitis (Corbera-Bellalta et al., 2016). Soluble CD14 from peripheral blood monocytes could be biological markers for screening and monitoring inflammatory disease activity in patients (Scherberich and Nockher, 1999).
CD36	Cluster of differentiation 36 molecule; fatty acid translocase	The CD36 encoded protein is the fourth major glycoprotein of the platelet surface and serves as a receptor for thrombospondin in platelets and various cell lines. This protein may have important functions as a cell adhesion molecule. It binds to collagen (Tandon et al., 1989), thrombospondin (Silverstein et al., 1992), anionic phospholipids and oxidized LDL (Podrez et al., 2002). CD36 is a key mediator of phagocytic oxLDL (oxidized low-density lipoprotein) uptake. CD36 was significantly reduced with plaque enriched long non-coding RNA in atherosclerotic macrophage regulation (PELATON) knockdown (Hung et al., 2020). CD36 (fatty acid translocase) as a key target gene for this miRNA and showed that the induced expression of CD36 is responsible for increased fatty acid uptake, thereby causing lipotoxicity in the heart (Li et al., 2019). The heat shock protein/glucocorticoid receptor (HSP/GR) complex-mediated CD36 axis was involved in the regulation of plaque formation in atherosclerosis development in mice (Silverstein et al., 1992). High-fat food-induced metabolic disorders promote lipoproteins accumulation, oxidative stresses, and active inflammation in macrophage of the vascular wall and accordingly result in the formation of atherosclerotic plaques by affecting the expression of GC, GR, HSP, CD36, and ABCA1 (cholesterol efflux regulatory protein) (Fu et al., 2019). CD36, a scavenger receptor, was at higher levels in the serum of patients with acute coronary syndrome or chronic coronary heart disease than in normal subjects (Bai et al., 2019). CD36 mediates foam cell formation and promotes inflammatory response and oxidative stress (Park, 2014; Xu et al., 2018) and promote atherosclerosis (Bai et al., 2019).