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Published on: September 15, 2018
Familial hypercholesterolemia and coronary heart disease: a HuGE association review
Melissa A Austin1, Carolyn M Hutter, Ron L Zimmern
1Institute for Public Health Genetics and Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, 1959 NE Pacific Avenue, Seattle, WA 98195, USA. maustin@u.washington.edu
Insights
Familial hypercholesterolemia (FH) is a genetic disorder causing high cholesterol and increasing heart disease risk. Gene mutations, like in LDLR and APOB, significantly impact FH severity and cardiovascular outcomes.
Area of Science:
- Genetics
- Cardiology
- Biochemistry
Background:
- Familial hypercholesterolemia (FH) is an autosomal disorder marked by elevated total cholesterol and low-density lipoprotein cholesterol (LDL-C).
- The FH phenotype is linked to heightened risks of coronary heart disease (CHD) and premature mortality.
- Genetic mutations, particularly in the low-density lipoprotein receptor gene (LDLR) and apolipoprotein B-100 gene (APOB), are key contributors to FH.
Purpose of the Study:
- To summarize the genetic basis of Familial hypercholesterolemia.
- To explore the relationship between specific gene mutations and FH phenotype severity.
- To review the association of FH with cardiovascular disease and the influence of other factors.
Main Methods:
- Review of existing literature on FH genetics and clinical presentation.
- Analysis of mutation types in LDLR and APOB genes.
- Examination of evidence linking FH to coronary heart disease.
Main Results:
- Mutations in LDLR can cause FH, with receptor-negative mutations leading to more severe phenotypes than receptor-defective ones.
- APOB gene mutations can mimic FH clinically and are associated with CHD.
- Preliminary data suggest other genetic and environmental factors influence the FH phenotype, but their interaction (synergistic or additive) is unclear.
Conclusions:
- FH is a significant genetic disorder with clear links to cardiovascular risk.
- Specific mutations in LDLR and APOB are major drivers of the FH phenotype and associated complications.
- Further research is needed to elucidate the complex interplay of genetic and environmental factors in FH.
Abstract:
Familial hypercholesterolemia (FH) is an autosomal disorder characterized by increased levels of total cholesterol and low density lipoprotein cholesterol. The FH clinical phenotype has been shown to be associated with increased coronary heart disease and premature death. Mutations in the low density lipoprotein receptor gene (LDLR) can result in the FH phenotype, and there is evidence that receptor-negative mutations result in a more severe phenotype than do receptor-defective mutations. Mutations in the apolipoprotein B-100 gene (APOB) can result in a phenotype that is clinically indistinguishable from familial hypercholesterolemia, and mutations in this gene have also been shown to be associated with coronary heart disease. Preliminary research indicates that the FH phenotype is influenced by other genetic and environmental factors; however, it is not clear if these are synergistic interactions or simply additive effects.
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