Plasma lipoproteins: genetic influences and clinical implications

Hegele, Robert A.

doi:10.1038/nrg2481

Cited by 472Lipoproteins and Cardiovascular HealthGenetic Associations and EpidemiologyLipid metabolism and disorders

Plasma lipoproteins: genetic influences and clinical implications

Hegele, Robert A.·2009·Nature Reviews Genetics

DOI 10.1038/nrg2481

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Abstract

Susceptibility to the growing global public health problem of cardiovascular disease is associated with levels of plasma lipids and lipoproteins. Several experimental strategies have helped us to clarify the genetic architecture of these complex traits, including classical studies of monogenic dyslipidaemias, resequencing, phenomic analysis and, more recently, genome-wide association studies and analysis of metabolic networks. The genetic basis of plasma lipoprotein levels can now be modelled as a mosaic of contributions from multiple DNA sequence variants, both rare and common, with varying effect sizes. In addition to filling gaps in our understanding of plasma lipoprotein metabolism, the recent genetic advances will improve our ability to classify, diagnose and treat dyslipidaemias.

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In humans and mice, genetic APOB variants associated with increased levels of apoB are also associated with unusually high plasma concentrations of cholesterol and LDL, which contribute to hypercholesterolemia and heart disease in humans.
“In humans and mice, genetic APOB variants associated with increased levels of apoB are also associated with unusually high plasma concentrations of cholesterol and LDL, which in turn contribute to hypercholesterolemia and heart disease in humans (Benn, 2009; Hegele, 2009).”
From Population genomics reveal recent speciation and rapid evolutionary adaptation in polar bears (2014) · cites this paper as Hegele, 2009

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The rationale for using apoA‐I as a clinical marker of cardiovascular risk
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Multiple Genetic Determinants of Variation of Plasma Lipoproteins in Alberta Hutterites
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An apolipoprotein A-V gene SNP is associated with marked hypertriglyceridemia among Asian-American patients*
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The value of HDL genetics
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APOA5 genetic variants are markers for classic hyperlipoproteinemia phenotypes and hypertriglyceridemia
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Functional characterization of genetic variants in NPC1L1 supports the sequencing extremes strategy to identify complex trait genes
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Levels of apolipoprotein M are not associated with the risk of coronary heart disease in two independent case-control studies
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What can the genome tell us about LDL cholesterol?
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Power and instrument strength requirements for Mendelian randomization studies using multiple genetic variants
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Familial hypercholesterolaemia
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Excess of rare variants in genes identified by genome-wide association study of hypertriglyceridemia
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Population genomics reveal recent speciation and rapid evolutionary adaptation in polar bears
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Quantitative variability of 342 plasma proteins in a human twin population
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Olezarsen, Acute Pancreatitis, and Familial Chylomicronemia Syndrome
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Angiopoietin-like protein 3 governs LDL-cholesterol levels through endothelial lipase-dependent VLDL clearance
Adam, R. C., Mintah, I. J., Alexa-Braun, C. A., Shihanian, L. M., Lee, J. S., Banerjee, P., Hamon, S. C., Kim, H. I., Cohen, J. C., Hobbs, H. H., et al. (2020) · Journal of Lipid Research · doi:10.1194/jlr.ra120000888 · Cited by 208 · see citing works
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Transcriptional Profiling of Human Liver Identifies Sex-Biased Genes Associated with Polygenic Dyslipidemia and Coronary Artery Disease
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A Review Article on Hyperlipidemia: Types, Treatments and New Drug Targets
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Total apolipoprotein E levels and specific isoform composition in cerebrospinal fluid and plasma from Alzheimer’s disease patients and controls
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Clinical and biochemical features of different molecular etiologies of familial chylomicronemia
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Type 2 Diabetes Genetics: Beyond GWAS
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Hypertriglyceridemia in the genomic era: a new paradigm
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Plasma level of LDL-cholesterol at diagnosis is a predictor factor of breast tumor progression
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Genetic testing in dyslipidemia: A scientific statement from the National Lipid Association
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Brothers in Arms: ABCA1- and ABCG1-Mediated Cholesterol Efflux as Promising Targets in Cardiovascular Disease Treatment
Frambach, S. J. C. M., de Haas, R., Smeitink, J. A. M., Rongen, G. A. P. J. M., Rüssel, F. G. M., & Schirris, T. J. J. (2019) · Pharmacological Reviews · doi:10.1124/pr.119.017897 · Cited by 145 · see citing works
Systemic and ocular fluid compounds as potential biomarkers in age-related macular degeneration
Kersten, E., Paun, C. C., Schellevis, R. L., Hoyng, C. B., Delcourt, C., Lengyel, I., Pető, T., Ueffing, M., Klaver, C. C. W., Dammeier, S., et al. (2017) · Survey of Ophthalmology · doi:10.1016/j.survophthal.2017.05.003 · Cited by 142 · see citing works
Hypertriglyceridemia
Berberich, A. J., & Hegele, R. A. (2013) · Nutrients · doi:10.3390/nu5030981 · Cited by 141 · see citing works
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Emerging roles for cholesterol and lipoproteins in lung disease
Gowdy, K. M., & Fessler, M. B. (2012) · Pulmonary Pharmacology & Therapeutics · doi:10.1016/j.pupt.2012.06.002 · Cited by 137 · see citing works
Lipoproteins and lipoprotein mimetics for imaging and drug delivery
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Genome‐wide association study validation identifies novel loci for atherosclerotic cardiovascular disease
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Comprehensive Analysis of Genomic Variation in the LPA Locus and Its Relationship to Plasma Lipoprotein(a) in South Asians, Chinese, and European Caucasians
Lanktree, M. B., Anand, S. S., Yusuf, S., & Hegele, R. A. (2009) · Circulation Cardiovascular Genetics · doi:10.1161/circgenetics.109.907642 · Cited by 135 · see citing works
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Nutrigenomics in Cardiovascular Medicine
Corella, D., & Ordovas, J. M. (2009) · Circulation: Cardiovascular Genetics · doi:10.1161/circgenetics.109.891366 · Cited by 138 · see citing works
Genetic bases of hypertriglyceridemic phenotypes
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Update on the molecular biology of dyslipidemias
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LipidSeq: a next-generation clinical resequencing panel for monogenic dyslipidemias
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Genetics of atherosclerosis
Lusis, A. J. (2012) · Trends in Genetics · doi:10.1016/j.tig.2012.03.001 · Cited by 119 · see citing works
Interferon-Lambda Genotype and Low Serum Low-Density Lipoprotein Cholesterol Levels in Patients With Chronic Hepatitis C Infection
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ApoB-containing lipoproteins regulate angiogenesis by modulating expression of VEGF receptor 1
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Dissecting lipid metabolism alterations in SARS-CoV-2
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Treatment Strategy for Dyslipidemia in Cardiovascular Disease Prevention: Focus on Old and New Drugs
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GPR146 Deficiency Protects against Hypercholesterolemia and Atherosclerosis
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Genetics of Triglycerides and the Risk of Atherosclerosis
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The Empirical Power of Rare Variant Association Methods: Results from Sanger Sequencing in 1,998 Individuals
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Targeted next-generation sequencing in monogenic dyslipidemias
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Transient Infantile Hypertriglyceridemia, Fatty Liver, and Hepatic Fibrosis Caused by Mutated GPD1, Encoding Glycerol-3-Phosphate Dehydrogenase 1
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Kiwifruit: our daily prescription for health
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A gut-derived hormone regulates cholesterol metabolism
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Authors: Hegele, R. A.
Affiliations: Western University (CA)
Corresponding author: Hegele, Robert A.
ORCID: Hegele, Robert A.
Venue: Nature Reviews Genetics
Publisher: Springer Science and Business Media LLC
Published: 2009-02
Volume: 10
Issue: 2
Pages: 109-121
ISSN: 1471-0056 (ISSN-L)
1471-0064
DOI: 10.1038/nrg2481
OpenAlex: W2068700927
Cited by: 462
References: 107
Citations by year: 2026: 10 · 2025: 11 · 2024: 19 · 2023: 21 · 2022: 32 · 2021: 22 · 2020: 24 · 2019: 19 · 2018: 27 · 2017: 19 · 2016: 31 · 2015: 33 · 2014: 36 · 2013: 26 · 2012: 31
FWCI: 7.03
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Reviews Genetics (publishedVersion)
PubMed (publishedVersion)
Scholarship@Western (Western University) (submittedVersion)
Topics: Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Keywords: serum lipoproteins, plasma lipids, genetic architecture, cardiovascular risk, dyslipidemia, genome-wide association study, rare variants, lipid metabolism, metabolic networks, phenomics, resequencing, disease diagnosis and treatment
MeSH terms: Animals, Cholesterol, Humans, Hyperlipoproteinemias, Lipoproteins, Models, Biological, Triglycerides, Genomics, Dyslipidemias

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Plasma lipoproteins: genetic influences and clinical implications

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