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Common and rare ABCA1 variants affecting plasma HDL cholesterol
1John P. Robarts Research Institute, London, Ontario, Canada.
Arteriosclerosis, Thrombosis, and Vascular Biology
|August 11, 2000
Summary
Common variations in the ABCA1 gene influence high-density lipoprotein (HDL) cholesterol levels in the general population. This study identified novel ABCA1 variants and confirmed their role in determining HDL cholesterol concentrations.
Area of Science:
- Genetics
- Molecular Biology
- Cardiovascular Disease
Background:
- Mutations in the ATP-binding cassette transporter A1 (ABCA1) gene cause Tangier disease and familial hypoalphalipoproteinemia, characterized by low high-density lipoprotein (HDL) cholesterol.
- The impact of common ABCA1 variants on HDL cholesterol in the general population remains unclear.
Purpose of the Study:
- To develop a screening strategy for identifying common ABCA1 variants.
- To investigate the association between common ABCA1 variants and plasma HDL cholesterol levels.
Main Methods:
- Developed a novel screening strategy using long-range amplification and deep sequencing of ABCA1 coding sequences and introns.
- Identified novel rare mutations and common silent and amino acid variants in the ABCA1 gene.
- Assessed the association of the ABCA1 I/M823 variant with HDL cholesterol in Canadian Inuit individuals.
Main Results:
- Discovered three novel ABCA1 mutations, including a frameshift and two missense mutations.
- Characterized four novel common amino acid variants and five novel common silent variants in ABCA1.
- Found that M823/M823 homozygotes for the ABCA1 I/M823 variant exhibited significantly higher plasma HDL cholesterol levels compared to other genotypes.
Conclusions:
- The developed screening approach is effective for identifying both rare and common ABCA1 genomic variants.
- Common amino acid variations within the ABCA1 gene are significant determinants of plasma HDL cholesterol levels in the general population.