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A Familial Hypercholesterolemia Human Liver Chimeric Mouse Model Using Induced Pluripotent Stem Cell-derived Hepatocytes
Published on: September 15, 2018
Familial occurrence of abnormalities of high-density lipoprotein cholesterol
1The Johns Hopkins Sibling and Family Heart Study, Department of Medicine, The Johns Hopkins Medical Institutions, 1830 East Monument Street, Room 8033, Baltimore, MD 21205, USA.
Insights
High-density lipoprotein cholesterol (HDL-C) levels are highly heritable, with genetic factors playing a significant role in HDL abnormalities and cardiovascular disease risk. Future genetic studies aim to identify HDL trait loci for improved therapies.
Area of Science:
- Genetics
- Cardiovascular Disease
- Biochemistry
Background:
- High-density lipoprotein cholesterol (HDL-C) disorders, both monogenic and polygenic, impact atherosclerotic disease risk.
- HDL-C levels exhibit significant heritability, accounting for 40-60% of individual variation in the general population.
- Understanding HDL-C genetics is crucial for managing cardiovascular health.
Purpose of the Study:
- To review known monogenic HDL disorders and HDL-C heritability.
- To present novel data on HDL-C heritability in families with premature coronary artery disease.
- To explore the genetic control of HDL-C levels and abnormalities.
Main Methods:
- Review of existing literature on monogenic HDL disorders and population heritability studies.
- Analysis of novel data on HDL-C heritability in families with a history of premature coronary artery disease.
- Assessment of genetic versus environmental/behavioral influences on HDL-C levels.
Main Results:
- HDL-C levels and abnormalities are predominantly under genetic control.
- Environmental and behavioral factors have a modest impact on HDL-C levels.
- Monogenic disorders provide insights into HDL regulation genetics.
Conclusions:
- HDL-C levels and abnormalities are largely genetically determined.
- Moderate to high heritability estimates support the success of future genetic studies.
- Identifying HDL genetic trait loci can lead to therapies optimizing HDL's cardiovascular benefits.
Abstract:
In families, well-known monogenic high-density lipoprotein cholesterol (HDL-C) disorders characterized by extreme HDL-C levels on both ends of the continuum occur in multiple HDL pathways and can confer increased risk for atherosclerotic disease. Polygenic HDL-C variants have been more difficult to identify. In many family and twin studies in different populations, HDL-C levels have been shown to be highly heritable, explaining, on average, between 40% and 60% of between-individual variation. This review of abnormal HDL in families addresses known monogenic HDL disorders and HDL-C heritability in the general population, and presents novel data on the heritability of HDL-C in families with a history of premature coronary artery disease. We conclude that levels of HDL-C and HDL abnormalities are largely under genetic control and environmental and behavioral factors alone have only a modest impact. While rare, monogenic disorders offer considerable insight into the genetics of HDL regulation. Moderate to high heritability estimates across different family populations suggest that future genetic studies will be successful in identifying HDL genetic trait loci and that translational studies will ultimately lead to therapies that optimize the cardiovascular protective benefits of HDL.
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