Analysis of HDL-microRNA panel in heterozygous familial hypercholesterolemia subjects with LDL receptor null or defective mutation

Roberto Scicali,Francesco Purrello,Salvatore Piro,Laura Calabresi,Stefania Di Mauro,Agnese Filippello,Francesca Urbano,Alessandra Scamporrino,Chiara Pavanello,Alice Ossoli,Arianna Strazzella,Antonino Di Pino,Agata Maria Rabuazzo,Antonia Alberti

doi:10.1038/s41598-019-56857-2

Abstract

In the last years increasing attention has been given to the connection between genotype/phenotype and cardiovascular events in subjects with familial hypercholesterolemia (FH). MicroRNAs (miRs) bound to high-density lipoprotein (HDL) may contribute to better discriminate the cardiovascular risk of FH subjects. Our aim was to evaluate the HDL-miR panel in heterozygous FH (HeFH) patients with an LDLR null or defective mutation and its association with pulse wave velocity (PWV). We evaluated lipid panel, HDL-miR panel and PWV in 32 LDLR null mutation (LDLR-null group) and 35 LDLR defective variant (LDLR-defective group) HeFH patients. HDL-miR-486 and HDL-miR-92a levels were more expressed in the LDLR-null group than the LDLR-defective group. When we further stratified the study population into three groups according to both the LDLR genotype and history of ASCVD (LDLR-null/not-ASCVD, LDLR-defective/not-ASCVD and LDLR/ASCVD groups), both the LDLR/ASCVD and the LDLR-null/not-ASCVD groups had a higher expression of HDL-miR-486 and HDL-miR-92a than the LDLR-defective/not-ASCVD group. Finally, HDL-miR-486 and HDL-miR-92a were independently associated with PWV. In conclusion, the LDLR-null group exhibited HDL-miR-486 and HDL-miR-92a levels more expressed than the LDLR-defective group. Further studies are needed to evaluate these HDL-miRs as predictive biomarkers of cardiovascular events in FH.

Highlights

In the last years increasing attention has been given to the connection between genotype/phenotype and cardiovascular events in subjects with familial hypercholesterolemia (FH)
Partecipants were divided in two groups according to the LDL receptor (LDLR) genotype: 32 heterozygous FH (HeFH) patients with an LDLR null mutation (LDLR-null group) and 35 HeFH patients with an LDLR defective mutation (LDLR-defective group)
We examined the role of high-density lipoprotein (HDL)-miRs in HeFH subjects with an LDLR null or defective mutation; to our learning, no other studies explored HDL-miR panel in these FH subgroups

Summary

Introduction

In the last years increasing attention has been given to the connection between genotype/phenotype and cardiovascular events in subjects with familial hypercholesterolemia (FH). Several studies have shown that heterozygous FH (HeFH) subjects with an LDL receptor (LDLR) null mutation had an increased atherosclerotic burden with respect to HeFH subjects with an LDLR defective variant[18,19]. In this context, it may be helpful to evaluate the HDL-miR panel in HeFH subjects with a different LDLR genotype

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