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Age and residual cholesterol efflux affect HDL cholesterol levels and coronary artery disease in ABCA1 heterozygotes
S M Clee1, J J Kastelein, M van Dam
1Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada.
The Journal of Clinical Investigation
|November 22, 2000
Summary
Mutations in the ABCA1 gene cause Tangier disease and familial hypoalphalipoproteinemia, leading to low HDL cholesterol and increased coronary artery disease risk. These findings highlight ABCA1
Area of Science:
- Genetics
- Cardiovascular Disease
- Metabolic Disorders
Background:
- Mutations in the ABCA1 gene are linked to Tangier disease (TD) and familial hypoalphalipoproteinemia (FHA).
- These conditions are characterized by impaired cholesterol efflux and reduced high-density lipoprotein cholesterol (HDL-C).
Purpose of the Study:
- To identify ABCA1 mutations and examine the phenotype of heterozygotes.
- To investigate the relationship between ABCA1 mutations, HDL-C levels, cholesterol efflux, and coronary artery disease (CAD) risk.
Main Methods:
- Identification of 13 ABCA1 mutations in 11 families (5 TD, 6 FHA).
- Phenotypic examination of 77 individuals heterozygous for ABCA1 mutations.
- Analysis of HDL-C levels, triglyceride levels, cholesterol efflux, and CAD frequency.
Main Results:
- ABCA1 heterozygotes exhibit decreased HDL-C and increased triglycerides.
- Cholesterol efflux levels strongly correlate with HDL-C, explaining 82% of its variation.
- ABCA1 heterozygotes show a threefold increase in CAD frequency with earlier onset, particularly those with lower cholesterol efflux.
Conclusions:
- Impairment of ABCA1-mediated cholesterol efflux reduces HDL-C levels.
- Reduced reverse cholesterol transport due to ABCA1 mutations significantly increases CAD risk.
- Age is a modifier of the phenotype in ABCA1 heterozygotes.
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