Familial combined hyperlipidemia: An overview of the underlying molecular mechanisms and therapeutic strategies

Abstract

Among different types of dyslipidemia, familial combined hyperlipidemia (FCHL) is the most common genetic disorder, which is characterized by at least two different forms of lipid abnormalities: hypercholesterolemia and hypertriglyceridemia. FCHL is an important cause of cardiovascular diseases. FCHL is a heterogeneous condition linked with some metabolic defects that are closely associated with FCHL. These metabolic features include dysfunctional adipose tissue, delayed clearance of triglyceride‐rich lipoproteins, overproduction of very low‐density lipoprotein and hepatic lipids, and defect in the clearance of low‐density lipoprotein particles. There are also some genes associated with FCHL such as those affecting the metabolism and clearance of plasma lipoprotein particles. Due to the high prevalence of FCHL especially in cardiovascular patients, targeted treatment is ideal but this necessitates identification of the genetic background of patients. This review describes the metabolic pathways and associated genes that are implicated in FCHL pathogenesis. We also review existing and novel treatment options for FCHL. © 2019 IUBMB Life, 71(9):1221–1229, 2019

Improvement Effect of 5-Aminolevulinic Acid on Hyperlipidemia in Miniature Schnauzer Dogs: An Open Study in 5 Cases of One Pedigree

“…Lipid disorders may be due to primary or secondary factors in dogs, 2 although in this study, it is likely that primary causes played a great role in hyperlipidemia as the dogs were extremely closely related, middle or old-aged MS, and all had elevated T-TG and VLDL-TG. 1,2,11 Such familial (genetic) hyperlipidemia is very common in humans, 19 as well as dogs. Incidentally, sibpair linkage analysis has been conducted to identify the responsible genes of various familial diseases in human medicine, 20 but demands an enormous amount of time.…”

Transgelin: A New Gene Involved in LDL Endocytosis Identified by a Genome-wide CRISPR-Cas9 Screen

“…Patients with this lipid phenotype are often diagnosed as having the Familial combined hyperlipidemia. These patients are known to be at a marked increased risk of coronary artery disease, but a clear monogenic basis for this disorder is yet to be identified [42]. Hypermethylation of TAGLN promoter has been shown to decrease transgelin expression in tumor cells [43].…”

A Rare Double Heterozygous Mutation in Low-Density Lipoprotein Receptor and Apolipoprotein B-100 Genes in a Severely Affected Familial Hypercholesterolaemia Patient

“…Several further therapeutic approaches are under development, such as squalene synthase inhibitors, siRNA for PCSK9 or for APOB silencing, and antisense PCSK9. Moreover, selective LDL apheresis is available for severe heterozygous and homozygous patients [19]. Therefore, in selected cases, genetic analysis is essential to administrate the most effective therapeutic options mentioned above.…”