RNA-sequencing based gene variants observed in patients with hyperlipidemia and premature coronary heart disease: A preliminary study

Familial hypercholesterolemia (FH) is a genetic disorder characterized by markedly elevated low-density lipoprotein (LDL) cholesterol levels, which primarily progresses to premature or familial coronary heart disease (FH-CHD). This cross-sectional study included healthy controls (N) and patients with hyperlipidemia (H), FH, CHD, and FH-CHD. We attempted to explore gene variants shared in H, FH and FH-CHD using next-generation sequencing tool. The RNA-seq transcriptome profiling from the whole peripheral blood (n = 3/group) were analyzed. The results revealed 15 intersected gene variants between the H/FH and FH-CHD groups. Aligning and mapping on the coding regions showed significant high-impact variants in 6 of the 15 genes including MAFG , AKAP1 , TLR5 , CHUK, EMC10, and PLRG1. The significant high-impact variations included frameshift variants in CHUK and PLRG, stop-gain variation in TLR5 at the last intron, stop-lost variation in EMC10, and splice-acceptor and donor variants in MAFG and AKAP1 , respectively. Pathogenicity scoring (ACMG Criteria) interpreted that these variation effects are predicted to lose the gene functions. Based on reference databases without any validation, these gene variations are probably linked to atherogenesis and CHD development. Conclusively, our exploratory observed that MAFG , AKAP1 , TLR5 , CHUK, EMC10, and PLRG1 variants had higher impacts and might be related to premature CHD development. Further classification and functional validation of these genetic variations should be considered for the feasibility of using these gene variants as contributory predictors of the FH-CHD risk in hyperlipidemia patients. • Familial hyperlipidemia (FH) contributes familial coronary heart disease (FH-CHD). • RNA-seq analysis was used to explore variants in patients with H, FH, CHD, and FH-CHD. • The intersected variants in MAFG, AKAP1, TLR5, CHUK, EMC10, and PLRG1 were selected. • These variants may be related to atherogenesis and premature CHD development.