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Published on: October 12, 2017
Marked HDL deficiency and premature coronary heart disease
Ernst J Schaefer1, Raul D Santos, Bela F Asztalos
1Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Tufts University School of Medicine, Boston, Massachusetts 02111, USA. ernst.schaefer@tufts.edu
Insights
Marked HDL deficiency, caused by APOA1 gene defects, leads to premature coronary heart disease (CHD). Different genetic defects in high-density lipoprotein (HDL) result in varied clinical outcomes.
Area of Science:
- Cardiovascular Medicine
- Genetics
- Metabolic Disorders
Background:
- High-density lipoprotein (HDL) deficiency is linked to various health issues.
- Apolipoprotein A-I (apoA-I) is crucial for HDL function.
- Genetic mutations can significantly impact HDL levels and function.
Purpose of the Study:
- To review recent publications on marked human HDL deficiency.
- To explore the relationship between HDL, coronary heart disease (CHD), amyloidosis, immune response, and kidney disease.
- To understand the clinical phenotypes associated with different HDL defects.
Main Methods:
- Literature review of recent publications.
- Analysis of genetic mutations affecting APOA1 and related genes.
- Correlation of molecular defects with clinical manifestations.
Main Results:
- APOAI gene mutations (deletions, rearrangements, nonsense/frameshift) cause apoA-I deficiency, leading to marked HDL deficiency, premature CHD, and potential xanthomas.
- ApoA-I variants are associated with amyloidosis.
- Tangier disease (ATP-binding cassette transporter A1 mutations) results in defective cholesterol efflux, altered HDL, neuropathy, and premature CHD.
- Lecithin:cholesterol acyltransferase deficiency presents with specific HDL patterns, corneal opacities, anemia, proteinuria, and kidney failure.
Conclusions:
- Clinical phenotypes in marked HDL deficiency vary greatly based on the underlying genetic defect.
- Understanding these genetic underpinnings is crucial for predicting and managing associated diseases like CHD and kidney disease.
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.
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