Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2010 Aug;21(4):289-97.
doi: 10.1097/MOL.0b013e32833c1ef6.

Marked HDL deficiency and premature coronary heart disease

Ernst J Schaefer  1 , Raul D Santos, Bela F Asztalos
Affiliations
Review

Marked HDL deficiency and premature coronary heart disease

Ernst J Schaefer et al. Curr Opin Lipidol. 2010 Aug.

Abstract

Purpose of review: Our purpose is to review recent publications in the area of marked human HDL deficiency, HDL particles, coronary heart disease (CHD), amyloidosis, the immune response, and kidney disease.

Recent findings: Lack of detectable plasma apolipoprotein (apo) A-I can be due to DNA deletions, rearrangements, or nonsense or frameshift mutations within the APOA1 gene resulting in a lack of apoA-I secretion. Such patients have marked HDL deficiency, normal levels of triglycerides and LDL cholesterol, and can have xanthomas and premature CHD. ApoA-I variants with amino acid substitutions, especially in the region of amino acid residues 50-93 and 170-178, have been associated with amyloidosis. Patients with homozygous Tangier disease have defective cellular cholesterol efflux due to mutations in the adenosine triphosphate-binding cassette transporter A1, detectable plasma apoA-I levels and prebeta-1 HDL in their plasma. They have decreased LDL cholesterol levels and can develop neuropathy and premature CHD. Patients with lecithin: cholesterol acyltransferase deficiency have both prebeta-1 and alpha-4 HDL present in their plasma and develop corneal opacities, anemia, proteinuria, and kidney failure.

Summary: Patients with marked HDL deficiency can have great differences in their clinical phenotype depending on the underlying defect.

PubMed Disclaimer

Figures

Figure 1
Figure 1. In the left panel the plasma apoA-I pattern obtained after two-dimensional gel electrophoresis is shown. To the right a schematic diagram of all the A-I containing HDL particles is shown
Particles are separated by size (diameter in nm) in the vertical dimension and by charge in the horizontal dimension into particles of preβ, α, and preα mobility.
Figure 2
Figure 2. A composite of the HDL gel patterns is shown
A composite is shown of the HDL gel patterns observed in a normal subject (far left), a homozygote with apoA-I deficiency (second gel from left), a Tangier homozygote (third gel from left), and a homozygote with LCAT deficiency (fourth from left). Also shown are gels from patients with lipoprotein lipase (LPL) deficiency (fifth from left), hepatic lipase deficiency (second from right), and cholesteryl ester transfer protein (CETP) deficiency (farthest to the right).
Figure 3
Figure 3
In this figure we have depicted results obtained when apoA-I HDL gels are also immunoblotted with antibodies containing apoA-II (far left), apoA-IV (second from left), apoC-I (third from left), apoC-III (second from right) and apoE (far right)
Figure 4
Figure 4. Models of apoA-I containing HDL particles are shown
The two small particles, preβ-1 and α-4 HDL are discs containing apoA-I without apoA-II. Medium-sized α-3 and α-2 HDL are shown, which are spherical particles containing both apoA-I and apoA-II, with α-2 HDL also containing serum amyloid A protein. The large spherical α-1 HDL particle is also shown
Figure 5
Figure 5
Findings in homozygous familial apolipoprotein deficiency are shown: tubo-eruptive xanthomas (upper left), with microscopy (lower right); planar xanthomas in the wrist area (upper right), moderate corneal opacification (lower left), and a normal eye fundus (lower middle)
Figure 6
Figure 6
Computed tomographic image of the heart of a 39-year-old patient with homozygous familial apolipoprotein A-I deficiency indicating marked coronary calcification in the left anterior descending coronary artery is shown
Figure 7
Figure 7
Coronary angiography of a 39-year-old patient with homozygous apoA-I deficiency is shown documenting complete obstruction of the left anterior descending coronary artery
Figure 8
Figure 8. A multidetector 64 slice computed tomographic angiographic image of a 39-year-old patient with homozygous familial apoA-I deficiency with premature coronary artery is shown
The aorta was normal, but significant narrowing of the left anterior descending coronary artery and the diagonal branches were noted, and the right coronary artery was totally obstructed, with a vein graft to the distal right coronary artery
Figure 9
Figure 9
A photograph of the enlarged orange tonsils from a patient with homozygous Tangier disease is shown
Figure 10
Figure 10
Electron micrographs of the cholesteryl ester deposition in the macrophages in the tonsils, bone marrow, nerve cells, and smooth muscle cells in a patient with homozygous Tangier disease are shown
Figure 11
Figure 11
A coronary angiogram in a 56-year-old patient with homozygous Tangier disease is shown documenting the presence of significant coronary artery disease in the right and left anterior descending coronary arteries
Figure 12
Figure 12
A diagram depicting our view of HDL particle metabolism is shown
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Santos RD, Schaefer EJ, Asztalos BF, et al. Characterization of high density lipoprotein particles in familial apolipoprotein A-I deficiency. J Lipid Res. 2008;46:349–357. - PubMed
    1. Santos RD, Miname MH, Martinez LR, et al. Noninvasive detection of aortic and coronary atherosclerosis in homozygous familial hypercholesterolemia by 64 slice multidetector row computed tomography angiography. Atherosclerosis. 2008;197:910–915. - PubMed
    1. Santos RD, Miname L, Asztalos BF, et al. Clinical presentation, laboratory values, and coronary heart disease risk in marked high density lipoprotein deficiency states. J Clin Lipidol. 2008;2:237–247. - PMC - PubMed
    1. Wada M, Iso T, Asztalos BF, et al. Marked high density lipoprotein deficiency due to apolipoprotein A-I Tomioka (codon 138 deletion) Atherosclerosis. 2009;207:157–161. - PubMed
    1. Favari E, Calabresi L, Adorni MP, et al. Small discoidal prebeta1 HDL particles are efficient acceptors of cell cholesterol via ABCA1 and ABCG1. Biochemistry. 2009;48:11067–11074. - PubMed

Publication types

MeSH terms

Substances