Apolipoproteins: metabolic role and clinical biochemistry applications
Open accessAbstract
Lipoprotein metabolism is dependent on apolipoproteins, multifunctional proteins that serve as templates for the assembly of lipoprotein particles, maintain their structure and direct their metabolism through binding to membrane receptors and regulation of enzyme activity. The three principal functions of lipoproteins are contribution to interorgan fuel (triglyceride) distribution (by means of the fuel transport pathway), to the maintenance of the extracellular cholesterol pool (by means of the overflow pathway) and reverse cholesterol transport. The most important clinical application of apolipoprotein measurements in the plasma is in the assessment of cardiovascular risk. Concentrations of apolipoprotein B and apolipoprotein AI (and their ratio) seem to be better markers of cardiovascular risk than conventional markers such as total cholesterol and LDL-cholesterol. Apolipoprotein measurements are also better standardized than the conventional tests. We suggest that measurements of apolipoprotein AI and apolipoprotein B are included as a part of the specialist lipid profile. We also suggest that lipoprotein (a) should be measured as part of the initial assessment of dyslipidaemias because of its consistent association with cardiovascular risk. Genotyping of apolipoprotein E isoforms remains useful in the investigation of mixed dyslipidaemias. Lastly, the role of postprandial metabolism is increasingly recognized in the context of atherogenesis, obesity and diabetes. This requires better markers of chylomicrons, very-low-density lipoproteins and remnant particles. Measurements of apolipoprotein B48 and remnant lipoprotein cholesterol are currently the key tests in this emerging field.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
A one standard deviation increment of apolipoprotein A1 (Apo A1) is associated with a reduced hazard ratio of major cardiovascular events.
“A one SD increment of Apo A1 is associated with a reduced hazard ratio of major cardiovascular events [103, 104].”
From Estimating the Effect of Aerobic Exercise Training on Novel Lipid Biomarkers: A Systematic Review and Multivariate Meta-Analysis of Randomized Controlled Trials (2023) · cites this paper as [104]
The Introduction reports a lower relative risk of myocardial infarction for a one-SD change in ApoAI (RR 0.67). It also reports a lower hazard ratio for ApoAI in a mortality study (HR 0.48), but does not specify that this HR is per one-SD increment; after adjustment, ApoAI was not among the significant predictors of coronary heart disease death. The source therefore supports the inverse association, but not the precise claim of a reduced hazard ratio for major cardiovascular events per one-SD increment. (LLM, conf=0.86)
Experimental — accuracy not yet measuredApoE is a determinant of CVD risk and atherosclerosis.
“Similarly, apoE is a determinant of CVD risk and atherosclerosis.”
From Automated multiplex LC-MS/MS assay for quantifying serum apolipoproteins A-I, B, C-I, C-II, C-III, and E with qualitative apolipoprotein E phenotyping (2016) · cites this paper as [3]
The Introduction section, under “Apolipoprotein E and cardiovascular risk,” reports differing coronary-risk odds ratios by apoE genotype and says the association between apoE genotype and CVD is well documented. It also notes apoE production by macrophages in atherosclerotic lesions, but that passage does not establish that apoE determines atherosclerosis risk. (LLM, conf=0.84)
Experimental — accuracy not yet measuredA standard tool for diagnosing dysbetalipoproteinemia is apoE phenotyping on the basis of immunostaining of 3 major isoforms (apoE2, apoE3, and apoE4) or apoE genotyping.
“A standard tool for diagnosing dysbetalipoproteinemia is apoE phenotyping on the basis of immunostaining of 3 major isoforms (apoE2, apoE3, and apoE4) or apoE genotyping (3, 8, 9 ) .”
From Automated multiplex LC-MS/MS assay for quantifying serum apolipoproteins A-I, B, C-I, C-II, C-III, and E with qualitative apolipoprotein E phenotyping (2016) · cites this paper as [3]
The Introduction describes immunostaining to identify the three apoE isoforms and says genotyping is used to confirm a diagnosis of dysbetalipoproteinaemia. It describes phenotyping as an earlier detection method with a continuing role in identifying people at risk, not as a standard diagnostic tool for the condition. Page numbers are not available in our copy. (LLM, conf=0.85)
Experimental — accuracy not yet measuredApolipoprotein E (ApoE) is an important component of lipoprotein and plays a major role in the uptake of lipoproteins into cells through low-density lipoprotein receptors.
“Apolipoprotein E (ApoE) is an important component of lipoprotein and plays a major role in the uptake of lipoproteins into cells through low-density lipoprotein receptors [1].”
From Membranous Nephropathy-Like Apolipoprotein E Deposition Disease with Apolipoprotein E Toyonaka (Ser197Cys) and a Homozygous Apolipoprotein E2/2 (2018) · cites this paper as [1]
Other apolipoproteins are widely distributed across the lipoprotein subclasses and offer important information about underlying diagnosis and cardiovascular risk.
“Other apolipoproteins are widely distributed across the lipoprotein subclasses and offer important information about underlying diagnosis and cardiovascular risk (3) .”
From Automated multiplex LC-MS/MS assay for quantifying serum apolipoproteins A-I, B, C-I, C-II, C-III, and E with qualitative apolipoprotein E phenotyping (2016) · cites this paper as [3]
ApoB-48 is a specific measure of chylomicrons and their remnants.
“In addition, apoB-48 is a specific measure of chylomicrons and their remnants (2, 3) .”
From Automated multiplex LC-MS/MS assay for quantifying serum apolipoproteins A-I, B, C-I, C-II, C-III, and E with qualitative apolipoprotein E phenotyping (2016) · cites this paper as [3]
The relative population frequencies observed in this study correlated to known prevalences (apoE3 60%-70%; apoE4 15%-20%; apoE2 5%-10%).
“Notably, the relative population frequencies observed in this study correlated to known prevalences (frequency for apoE3, 60%-70%; apoE4, 15%-20%; and apoE2, 5%-10%) (3) .”
From Automated multiplex LC-MS/MS assay for quantifying serum apolipoproteins A-I, B, C-I, C-II, C-III, and E with qualitative apolipoprotein E phenotyping (2016) · cites this paper as [3]
ApoE polymorphisms are associated with other lipid abnormalities and neurological disorders such as Alzheimer disease.
“Moreover, apoE polymorphisms are associated with other lipid abnormalities and neurological disorders such as Alzheimer disease (3, 8, 9 ) .”
From Automated multiplex LC-MS/MS assay for quantifying serum apolipoproteins A-I, B, C-I, C-II, C-III, and E with qualitative apolipoprotein E phenotyping (2016) · cites this paper as [3]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A Receptor-Mediated Pathway for Cholesterol Homeostasis
Brown, M. S., & Goldstein, J. L. (1986) · Science · doi:10.1126/science.3513311 · Cited by 5,703 · see citing works
Nordestgaard, B. G., Benn, M., Schnohr, P., & Tybjærg-Hansen, A. (2007) · JAMA · doi:10.1001/jama.298.3.299 · Cited by 2,058 · see citing works
cDNA sequence of human apolipoprotein(a) is homologous to plasminogen
McLean, J. W., Tomlinson, J. E., Kuang, W.-J., Eaton, D. L., Chen, E. Y., Fless, G. M., Scanu, A. M., & Lawn, R. M. (1987) · Nature · doi:10.1038/330132a0 · Cited by 1,886 · see citing works
Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women
Bansal, S., Buring, J. E., Rifai, N., Mora, S., Sacks, F. M., & Ridker, P. M. (2007) · JAMA · doi:10.1001/jama.298.3.309 · Cited by 1,619 · see citing works
Atherogenic lipoprotein phenotype. A proposed genetic marker for coronary heart disease risk
Austin, M. A., King, M. C., Vranizan, K. M., & Krauss, R. M. (1990) · Circulation · doi:10.1161/01.cir.82.2.495 · Cited by 1,411 · see citing works
Relation of triglyceride metabolism and coronary artery disease. Studies in the postprandial state
Patsch, J. R., Miesenböck, G., Hopferwieser, T., Mühlberger, V, Knapp, E., Dunn, J. K., Gotto, A. M., & Patsch, W. (1992) · Arteriosclerosis and Thrombosis: A Journal of Vascular Biology · doi:10.1161/01.atv.12.11.1336 · Cited by 1,122 · see citing works
Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies
(2010) · The Lancet · doi:10.1016/s0140-6736(10)60545-4 · Cited by 716 · see citing works
Sacks, F. M., Alaupovic, P., Moye, L. A., Cole, T. G., Sussex, B., Stampfer, M. J., Pfeffer, M. A., & Braunwald, E. (2000) · Circulation · doi:10.1161/01.cir.102.16.1886 · Cited by 490 · see citing works
Apolipoprotein E polymorphism in health and disease
Utermann, G. (1987) · American Heart Journal · doi:10.1016/0002-8703(87)90610-7 · Cited by 389 · see citing works
Postprandial lipoprotein metabolism and atherosclerosis.
Karpe, F. (1999) · Journal of Internal Medicine · doi:10.1046/j.1365-2796.1999.00548.x · Cited by 360 · see citing works
Mechanism of plasma cholesteryl ester transfer in hypertriglyceridemia.
Mann, C. J., Yen, F. T., Grant, A. M., & Bihain, B. E. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115535 · Cited by 339 · see citing works
Contois, J. H., McConnell, J. P., Sethi, A. A., Csako, G., Devaraj, S., Hoefner, D. M., & Warnick, G. R. (2009) · Clinical Chemistry · doi:10.1373/clinchem.2008.118356 · Cited by 326 · see citing works
Liu, J., Sempos, C. T., Donahue, R. P., Dorn, J., Trevisan, M., & Grundy, S. M. (2006) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2006.06.032 · Cited by 277 · see citing works
Zambon, A., Hokanson, J. E., Brown, B. G., & Brunzell, J. D. (1999) · Circulation · doi:10.1161/01.cir.99.15.1959 · Cited by 263 · see citing works
THOMPSON, A., & DANESH, J. (2006) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2006.01644.x · Cited by 252 · see citing works
Cohn, J. S., Marcoux, C., & Davignon, J. (1999) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.19.10.2474 · Cited by 156 · see citing works
ApoE Plasma Levels and Risk of Cardiovascular Mortality in Old Age
Mooijaart, S. P., Berbée, J. F. P., van Heemst, D., Havekes, L. M., de Craen, A. J. M., Slagboom, P. E., Rensen, P. C. N., & Westendorp, R. G. J. (2006) · PLoS Medicine · doi:10.1371/journal.pmed.0030176 · Cited by 129 · see citing works
Austin, M. A., & Edwards, K. L. (1996) · Current Opinion in Lipidology · doi:10.1097/00041433-199606000-00010 · Cited by 126 · see citing works
Markers of triglyceride-rich lipoprotein remnant metabolism in visceral obesity
Chan, D. C., Watts, G. F., Barrett, P. H., Mamo, J. C., & Redgrave, T. G. (2002) · Clinical Chemistry · doi:10.1093/clinchem/48.2.278 · Cited by 117 · see citing works
Remnant lipoproteins as therapeutic targets
Havel, R. J. (2000) · Current Opinion in Lipidology · doi:10.1097/00041433-200012000-00008 · Cited by 107 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [1]1. Baynes J, Dominiczak MH, eds. Medical Biochemistry. 3rd edn. London: Elsevier Mosby, 2009:653 Go to Reference Crossref Google Scholar
Cited by
Sorted by citations
Postprandial hypertriglyceridemia as a coronary risk factor
Borén, J., Matikainen, N., Adiels, M., & Taskinen, M.-R. (2014) · Clinica Chimica Acta · doi:10.1016/j.cca.2014.01.015 · Cited by 182 · see citing works
van den Broek, I., Romijn, F. P. H. T. M., Nouta, J., van der Laarse, A., Drijfhout, J. W., Smit, N. P. M., van der Burgt, Y. E. M., & Cobbaert, C. M. (2016) · Clinical Chemistry · doi:10.1373/clinchem.2015.246702 · Cited by 105 · see citing works
Borén, J., Watts, G. F., Adiels, M., Söderlund, S., Chan, D. C., Hakkarainen, A., Lundbom, J., Lundbom, N., Matikainen, N., Kahri, J., et al. (2015) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.115.305614 · Cited by 72 · see citing works
Apolipoproteins: New players in cancers
He, Y., Chen, J., Ma, Y., & Chen, H. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.1051280 · Cited by 52 · see citing works
Kinetics of plasma apolipoprotein E isoforms by LC-MS/MS: a pilot study
Blanchard, V., Ramin-Mangata, S., Billon-Crossouard, S., Aguesse, A., Durand, M., Chemello, K., Nativel, B., Flet, L., Chétiveaux, M., Jacobi, D., et al. (2018) · Journal of Lipid Research · doi:10.1194/jlr.p083576 · Cited by 43 · see citing works
Plasma proteome and metabolome characterization of an experimental human thyrotoxicosis model
Pietzner, M., Engelmann, B., Kacprowski, T., Golchert, J., Dirk, A.-L., Hammer, E., Iwen, K. A., Nauck, M., Wallaschofski, H., Führer, D., et al. (2017) · BMC Medicine · doi:10.1186/s12916-016-0770-8 · Cited by 40 · see citing works
Wood, G., Taylor, E., Ng, V., Murrell, A., Patil, A., van der Touw, T., Wolden, M., Andronicos, N., & Smart, N. A. (2023) · Sports Medicine · doi:10.1007/s40279-023-01817-0 · Cited by 31 · see citing works
“A one SD increment of Apo A1 is associated with a reduced hazard ratio of major cardiovascular events [103, 104].”
BackgroundFukunaga, M., Nagahama, K., Aoki, M., Shimizu, A., Hara, S., Matsunaga, A., Muso, E., & Saito, T. (2018) · Case Reports in Nephrology and Dialysis · doi:10.1159/000487919 · Cited by 14 · see citing works
- Authors
- Dominiczak, M. H., & Caslake, M. J.
- Affiliations
- NHS Greater Glasgow and Clyde (GB)
- Western Infirmary (GB)
- Corresponding author
- Dominiczak, Marek H
- Venue
- Annals of Clinical Biochemistry: International Journal of Laboratory Medicine
- Publisher
- SAGE Publications
- Published
- 2011-10-25
- Volume
- 48
- Issue
- 6
- Pages
- 498-515
- ISSN
- 0004-5632 (ISSN-L)
- 1758-1001
- OpenAlex
- W1993718080
- Cited by
- 238
- References
- 20
- Citations by year
- 2026: 13 · 2025: 23 · 2024: 18 · 2023: 26 · 2022: 28 · 2021: 28 · 2020: 21 · 2019: 13 · 2018: 16 · 2017: 7 · 2016: 11 · 2015: 7 · 2014: 9 · 2013: 11 · 2012: 5
- FWCI
- 1.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Annals of Clinical Biochemistry International Journal of Laboratory Medicine (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- apolipoproteins, lipoprotein metabolism, apolipoprotein A-I, apolipoprotein B, lipoprotein(a), cardiovascular risk assessment, dyslipidemia, remnant cholesterol, apolipoprotein B-48, postprandial lipoproteins, chylomicrons, VLDL, atherogenesis, obesity, diabetes mellitus
- MeSH terms
- Animals, Apolipoproteins, Cardiovascular Diseases, Diabetes Mellitus, Humans, Insulin Resistance, Obesity, Biomarkers, Postprandial Period, Protein Isoforms, Metabolic Syndrome, Lipid Metabolism Disorders
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
