Genetic Causes of Monogenic Heterozygous Familial Hypercholesterolemia: A HuGE Prevalence Review
Abstract
The clinical phenotype of heterozygous familial hypercholesterolemia (FH) is characterized by increased plasma levels of total cholesterol and low density lipoprotein cholesterol, tendinous xanthomata, and premature symptoms of coronary heart disease. It is inherited as an autosomal dominant disorder with homozygotes having a more severe phenotype than do heterozygotes. FH can result from mutations in the low density lipoprotein receptor gene (LDLR), the apolipoprotein B-100 gene (APOB), and the recently identified proprotein convertase subtilisin/kexin type 9 gene (PCSK9). To date, over 700 variants have been identified in the LDLR gene. With the exception of a small number of founder populations where one or two mutations predominate, most geographically based surveys of FH subjects show a large number of mutations segregating in a given population. Studies of the prevalence of FH would be improved by the use of a consistent and uniformly applied clinical definition. Because FH responds well to drug treatment, early diagnosis to reduce atherosclerosis risk is beneficial. Cascade testing of FH family members is cost effective and merits further research. For screening to be successful, public health and general practitioners need to be aware of the signs and diagnosis of FH and the benefits of early treatment.
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The FH patients used to build the classifier were diagnosed as probable or definite FH using existing diagnostic criteria including genetic testing information when available.
“The FH patients were followed at an FH-specific clinic and had been diagnosed as probable or definite FH using existing diagnostic criteria including genetic testing information when available.5,33–36”
From Finding missed cases of familial hypercholesterolemia in health systems using machine learning (2019) · cites this paper as [35]
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- Authors
- Austin, M. A.
- Affiliations
- University of Washington (US)
- Corresponding author
- Austin, M. A.
- Venue
- American Journal of Epidemiology
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-09-01
- Volume
- 160
- Issue
- 5
- Pages
- 407-420
- ISSN
- 0002-9262 (ISSN-L)
- OpenAlex
- W2104211766
- Cited by
- 657
- References
- 3
- Citations by year
- 2026: 11 · 2025: 36 · 2024: 34 · 2023: 28 · 2022: 55 · 2021: 41 · 2020: 37 · 2019: 50 · 2018: 50 · 2017: 56 · 2016: 36 · 2015: 32 · 2014: 27 · 2013: 28 · 2012: 29
- FWCI
- 2.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Epidemiology (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- British Heart Foundation
- National Institutes of Health (2r01hl049513-08)
- Centers for Disease Control and Prevention (U36 CCU 300430-22, U36/CCU300430-20)
- National Heart, Lung, and Blood Institute (HL 49513)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- heterozygous familial hypercholesterolemia, LDLR mutations, PCSK9 gene, genetic factors, prevalence, clinical definition, cascade testing, early diagnosis, cardiovascular risk, atherosclerosis, LDL cholesterol
- MeSH terms
- Adult, Female, Genetics, Population, Humans, Hyperlipoproteinemia Type II, Male, Middle Aged, Phenotype, Receptors, LDL, Prevalence
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