Homozygous familial hypercholesterolemia (
HoFH) is a rare, life-threatening
genetic disorder characterized by an extremely elevated serum level of
low-density lipoprotein cholesterol (
LDL-C) and accelerated premature atherosclerotic
cardiovascular diseases (ASCVD). However, the detailed mechanism of how the pathogenic mutations of
HoFH trigger the acceleration of ASCVD is not well understood. Therefore, we performed high-throughput
RNA and small
RNA sequencing on the peripheral blood
RNA samples of six
HoFH patients and three healthy controls. The gene and
miRNA expression differences were analyzed, and seven
miRNAs and six corresponding genes were screened out through regulatory network analysis. Validation through quantitative PCR of genes and
miRNAs from 52
HoFH patients and 20 healthy controls revealed that the expression levels of hsa-miR-486-3p,
hsa-miR-941, and BIRC5 were significantly upregulated in
HoFH, while ID1, PLA2G4C, and CACNA2D2 were downregulated. Spearman correlation analysis found that the levels of ID1,
hsa-miR-941, and hsa-miR-486-3p were significantly correlated with additional ASCVD risk factors in
HoFH patients. This study represents the first integrated analysis of transcriptome and
miRNA expression profiles in patients with
HoFH, a
rare disease, and as a result, six differentially expressed
miRNAs/genes that may be related to
atherosclerosis in
HoFH are reported. The
miRNA-
mRNA regulatory network may be the critical regulation mechanism by which ASCVD is accelerated in
HoFH.