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.
“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]
The introduction (p. 495) reports that the small, dense LDL phenotype was associated with increased myocardial infarction risk, consistent with two previous studies. But the paper does not say that epidemiological studies vary in their findings about an independent association of large or small LDL with cardiovascular disease. Its multivariate analysis examines associations with LDL phenotype, not independent associations with disease. (LLM, conf=0.82)
Experimental — accuracy not yet measuredFasting triglyceride levels from as low as approximately 1.2 mmol/L can be associated with a cluster of metabolic abnormalities that include accumulation of triglyceride-rich lipoproteins and remnants, as well as increased cardiovascular disease events.
“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).”
Triglyceride-rich lipoproteins and triglyceride-rich lipoprotein remnants accumulate in plasma at fasting triglyceride levels above 1.2 mmol/L.
“TRL and TRL remnants accumulate in the plasma at fasting TG levels >1.2 mmol/L (>100 mg/dL).”
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- 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 › Surgery › 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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