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Updated: Aug 26, 2025
A Familial Hypercholesterolemia Human Liver Chimeric Mouse Model Using Induced Pluripotent Stem Cell-derived Hepatocytes
Published on: September 15, 2018
Genetic and molecular architecture of familial hypercholesterolemia
Marianne Abifadel1,2, Catherine Boileau1,3
1UMR1148, Inserm, Hôpital Bichat-Claude Bernard, 46 rue Henri Huchard, F-75018 Paris, France.
Insights
Familial hypercholesterolemia (FH), a genetic condition causing high cholesterol, is underdiagnosed globally. Early diagnosis and accessible treatments for FH are crucial to prevent premature cardiovascular disease and reduce patient burden.
Area of Science:
- Cardiology
- Genetics
- Public Health
Background:
- Atherosclerotic cardiovascular disease is the leading global cause of mortality.
- Familial hypercholesterolemia (FH) significantly increases the risk of premature atherosclerosis and cardiovascular disease.
- Despite its prevalence, FH remains largely underdiagnosed worldwide.
Purpose of the Study:
- To highlight the genetic basis of Familial hypercholesterolemia (FH).
- To review advancements in the diagnosis and treatment of FH.
- To emphasize the need for improved accessibility of FH prevention, diagnosis, and treatment.
Main Methods:
- Genetic analysis of genes including LDLR, APOB, PCSK9, APOE, and LDLRAP1.
- Review of clinical diagnostic tools and therapeutic advancements.
- Analysis of the impact of genetic discoveries and pharmacological interventions.
Main Results:
- Identified key genes (LDLR, APOB, PCSK9, APOE, LDLRAP1) responsible for FH.
- Demonstrated significant progress in diagnostic tools and therapeutic options over the last two decades.
- Highlighted the role of genetic discoveries (e.g., LDLR, PCSK9) and treatments (e.g., statins, PCSK9 inhibitors) in managing FH.
Conclusions:
- Genetic discoveries have revolutionized FH diagnosis and treatment.
- Continued advancements in diagnostics and therapeutics offer improved management strategies.
- Enhancing the accessibility of prevention, diagnosis, and treatment is vital to mitigate the lifelong impact of FH.
Abstract:
Atherosclerotic cardiovascular disease is the leading cause of death globally. Despite its important risk of premature atherosclerosis and cardiovascular disease, familial hypercholesterolemia (FH) is still largely underdiagnosed worldwide. It is one of the most frequently inherited diseases due to mutations, for autosomal dominant forms, in either of the LDLR, APOB, and PCSK9 genes or possibly a few mutations in the APOE gene and, for the rare autosomal forms, in the LDLRAP1 gene. The discovery of the genes implicated in the disease has largely helped to improve the diagnosis and treatment of FH from the LDLR by Brown and Goldstein, as well as the introduction of statins, to PCSK9 discovery in FH by Abifadel et al., and the very rapid availability of PCSK9 inhibitors. In the last two decades, major progress has been made in clinical and genetic diagnostic tools and the therapeutic arsenal against FH. Improving prevention, diagnosis, and treatment and making them more accessible to all patients will help reduce the lifelong burden of the disease.
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