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Atherogenic lipoprotein phenotype. A proposed genetic marker for coronary heart disease risk
Open accessAbstract
In a community-based study of 301 subjects from 61 nuclear families, two distinct phenotypes (denoted A and B) were identified by nondenaturing gradient gel electrophoretic analysis of low density lipoprotein (LDL) subclasses. Phenotype A was characterized by predominance of large, buoyant LDL particles, and phenotype B consisted of a major peak of small, dense LDL particles. Previous analysis of the family data by complex segregation analysis demonstrated that these phenotypes appear to be inherited as a single-gene trait. In the present study, the phenotypes were found to be closely associated with variations in plasma levels of other lipid, lipoprotein, and apolipoprotein measurements. Specifically, phenotype B was associated with increases in plasma levels of triglyceride and apolipoprotein B, with mass of very low and intermediate density lipoproteins, and with decreases in high density lipoprotein (HDL) cholesterol, HDL2 mass, and plasma levels of apolipoprotein A-I. Thus, the proposed genetic locus responsible for LDL subclass phenotypes also results in an atherogenic lipoprotein phenotype.
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“Epidemiological studies vary as to the independent association between large or small LDL and atherosclerotic cardiovascular disease (30).”
From Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline (2012) · cites this paper as [30]
Experimental — accuracy not yet measuredIn the citing paper
“it is less widely appreciated that fasting levels from as low as ∼1.2 mmol/L (∼100 mg/dL) can be associated with a cluster of metabolic abnormalities that include accumulation of TRL and remnants,14 as well as increased cardiovascular disease events15,16 (Figure 1).”
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“TRL and TRL remnants accumulate in the plasma at fasting TG levels >1.2 mmol/L (>100 mg/dL).”
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Berglund, L., Brunzell, J. D., Goldberg, A. C., Goldberg, I. J., & Stalenhoef, A. (2014) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2013.10.002 · Cited by 50
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Hypothyroidism Results in Small Dense LDL Independent of IRS Traits and Hypertriglyceridemia
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Polyacrylamide Gradient Gel Electrophoresis of Lipoprotein Subclasses
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Reversal of Small, Dense LDL Subclass Phenotype by Normalization of Adiposity
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“Overweight and obesity have been associated with an atherogenic lipoprotein phenotype (ALP) that is characterized by elevated triacylglycerols (TGs), reduced high-density lipoprotein (HDL) cholesterol and increased concentrations of small, dense low-density lipoprotein (LDL subclass pattern B) (1,2).”
BackgroundSelf-citationPlasma Lipoproteins and Triacylglycerol are Predictors of Small, Dense LDL Particles
Tsimihodimos, V., Gazi, I. F., Kostara, C. E., Tselepis, A. D., & Elisaf, M. (2007) · Lipids · doi:10.1007/s11745-007-3050-8 · Cited by 42
Autoantibodies to oxidized LDL and cardiovascular risk: The Framingham Offspring Study
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“Observational studies and clinical trials have repeatedly hown that the plasma concentration of low density lipoproein (LDL) cholesterol is a key factor in the development f clinical arteriosclerosis [1,2] Interest in risk factors for therosclerosis and cardiovascular disease events has now rogressed to assessing aspe…”
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“These particles have shown to be prevalent in patients with CAD [18–24].”
BackgroundGenetics of LDL particle heterogeneity: from genetic epidemiology to DNA-based variations.
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“LDL size: a component of the metabolic syndrome and a trait representing a common atherogenic lipoprotein profile The metabolic syndrome is characterized by a cluster of CAD risk factors, including hypertension, upper body obesity, glucose intolerance, and the atherogenic lipoprotein phenotype, which consists of incre…”
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The effect of n−3 fatty acids on low density lipoprotein subfractions
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“Also, TG:HDL-C [19] and oxLDL:LDL-C [20] ratios were calculated.”
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“[33] subjects were classified as phenotypes A (large particle size; 26.”
BackgroundTriacylglycerol and coronary heart disease
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Metadata
- Authors
- Austin, M. A., King, M. C., Vranizan, K. M., & Krauss, R. M.
- Affiliations
- University of California, Berkeley (US)
- ORCID
- Venue
- Circulation
- Published
- 1990-08
- Volume
- 82
- Issue
- 2
- Pages
- 495-506
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2089286420
- Cited by
- 1,411
- References
- 63
- Citations by year
- 2026: 11 · 2025: 15 · 2024: 17 · 2023: 39 · 2022: 20 · 2021: 26 · 2020: 25 · 2019: 27 · 2018: 17 · 2017: 21 · 2016: 27 · 2015: 42 · 2014: 38 · 2013: 46 · 2012: 39
- FWCI
- 47.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Energy (DE-AC03-?, AC03-76SF00098, DEAC03-76SF00098)
- National Institutes of Health (7r29hl038760-03, 5p01hl018574-26, DE-AC03- 76SF00098)
- National Heart, Lung, and Blood Institute (HL38760, HL-18574)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- atherogenic lipoprotein phenotype, LDL subclasses, low-density lipoprotein, coronary heart disease risk, genetic markers, single-gene inheritance, apolipoprotein B, apolipoprotein A-I, HDL cholesterol, HDL2, triglycerides, VLDL, intermediate density lipoprotein
- MeSH terms
- Adolescent, Adult, Aged, Arteriosclerosis, Child, Child, Preschool, Chromosome Mapping, Coronary Disease, Female, Genetic Markers, Humans, Lipids, Lipoproteins, Cholesterol, HDL, Male, Middle Aged, Phenotype, Risk Factors, Triglycerides, Multivariate Analysis
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