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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]
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“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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Long‐chain n‐3 polyunsaturated fatty acids and triacylglycerol metabolism in the postprandial state
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Low Density Lipoprotein Particle Size and Risk of Early-Onset Myocardial Infarction in Women
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“The interrelations between triglyceride, HDL cholesterol, and LDL particle size may reflect the “atherogenic lipoprotein phenotype” (32), in which small, dense LDL is associated with a variety of other lipoprotein risk factors, including increased plasma triglyceride, increased apolipoprotein B, lower HDL cholesterol,…”
BackgroundWomen have a larger and less atherogenic low density lipoprotein particle size than men
Nikkilä, M. T., Pitkäjärvi, T., Koivula, T. A., Solakivi, T., Lehtimäki, T. J., Laippala, P. J., Jokela, H., Lehtom̈aki, E., Seppä, K., & Sillanaukee, P. (1996) · Atherosclerosis · doi:10.1016/0021-9150(95)05645-9 · Cited by 59
High Dietary Fructose Intake on Cardiovascular Disease Related Parameters in Growing Rats
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“Also, chronic exposure of dyslipidemia has a major effect on cardiovascular disease (CVD) [15].”
BackgroundA unique genetic and biochemical presentation of fish-eye disease.
Kuivenhoven, J. A., Voorst, E. V. V. T., Wiebusch, H., Marcovina, S. M., Funke, H., Assmann, G., Pritchard, P. H., & Kastelein, J. J. P. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118348 · Cited by 58
LDL subfractions in acromegaly: relation to growth hormone and insulin-like growth factor-I
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“Sd-LDL is a risk factor for the development of coronary artery disease in Westerners [4,5] and Japanese with relatively low LDL cholesterol concentrations [6,7].”
BackgroundAtherogenic Dyslipidemia in Latin America: Prevalence, causes and treatment
Ponte-Negretti, C. I., Isea-Perez, J. E., Lorenzatti, A. J., López-Jaramillo, P. A., Wyss-Q, F. S., Pintó, X., Lanas, F. T., Medina, J., Machado-H, L. T., Mónica Acevedo, B., et al. (2017) · International Journal of Cardiology · doi:10.1016/j.ijcard.2017.05.059 · Cited by 66
Low density lipoprotein particle diameter in young, nonobese, normolipidemic Japanese men
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Naringin Ameliorates Atherogenic Dyslipidemia but not Hyperglycemia in Rats With Type 1 Diabetes
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A 16-week fenofibrate treatment increases LDL particle size in type IIA dyslipidemic patients.
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“Among others, the presence of small, dense LDL particles have been associated with elevated triglyceride (TG) levels and reduced high density lipoprotein (HDL) cholesterol concentrations [16,18,20] as well as an increased ratio of total cholesterol/HDL cholesterol, a lipid index commonly used to globally estimate CHD…”
BackgroundFunctional food science and substrate metabolism
Saris, W. H. M., L., N. G., Björck, I., Blaak, E. E., Bornet, F. R. J., Brouns, F. J. P. H., Frayn, K. N., Fürst, P., Riccardi, G., Roberfroid, M. B., et al. (1998) · British Journal Of Nutrition · doi:10.1079/bjn19980105 · Cited by 55
“There is evidence for a genetic component (Austin et al. 1990; Mitchell et al. 1996).”
BackgroundShikuma, C. M., Yang, Y., Glesby, M. J., Meyer, W. A., Tashima, K. T., Ribaudo, H. J., Webb, N., Bastow, B., Kuritzkes, D. R., & Gulick, R. M. (2007) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/qai.0b013e318031d5a0 · Cited by 55
The metabolic basis of atherogenic dyslipidemia
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“* emia because they are: (1) primary features of this form of dyslipidemia; (2) associated with insulin resistance, detectable early in the development of the metabolic syndrome; (3) individually highly inherited; and (4) relatively simple to quantify.”
BackgroundLipoprotein subclasses and atherosclerosis.
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“Although the relationship of LDL particle size to atherosclerosis in monkeys may be species- and diet-dependent, the present study in rhesus monkeys is consistent with reports in humans that lower plasma TG are associated with less atherogenic LDL (28-30,32).”
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Oxidation of low density lipoprotein in patients on regular haemodialysis
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All Low-Density Lipoprotein Particles Are Not Created Equal
Krauss, R. M. (2014) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.114.303458 · Cited by 55
Self-citation
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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