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Updated: May 14, 2026

Isolation and Analysis of Plasma Lipoproteins by Ultracentrifugation
Published on: January 28, 2021
Identification of a functional apolipoprotein E promoter polymorphism regulating plasma apolipoprotein E
Maria Nastase Mannila1, Hovsep Mahdessian, Anders Franco-Cereceda
1Cardiovascular Genetics and Genomics Group, Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Researchers identified a genetic variant, rs769446, in the apolipoprotein E (APOE) promoter that regulates plasma APOE concentration. This finding sheds light on the genetic factors influencing APOE levels in individuals.
Area of Science:
- Genetics
- Molecular Biology
- Cardiovascular Research
Background:
- Plasma apolipoprotein E (APOE) concentration and APOE genotype influence lipoprotein levels.
- Functional genetic variants affecting plasma APOE concentration remain largely unidentified.
Purpose of the Study:
- To identify functional genetic variants that influence plasma apolipoprotein E (APOE) concentration.
- To investigate the role of the APOE locus in regulating APOE levels.
Main Methods:
- Genome-wide association studies (GWAS) in two cohorts.
- Fine-mapping of the APOE locus.
- Expression studies in human liver samples.
- Transient transfection and electrophoretic mobility shift assays in HepG2 cells.
Main Results:
- The APOE locus was the only genetic locus robustly associated with plasma APOE concentration.
- The rs7412 ε2-allele was confirmed as a primary genetic determinant of plasma APOE concentration.
- The APOE promoter variant rs769446 (-427T/C) was independently associated with plasma APOE concentration.
- The rs769446 C-allele correlated with increased APOE mRNA levels and demonstrated a role in APOE transcriptional regulation.
- No association was found between rs769446 genotype and plasma lipoprotein levels in APOE ε3/ε3 carriers.
Conclusions:
- rs769446 is a functional polymorphism that regulates plasma APOE concentration.
- This variant influences APOE mRNA levels and transcriptional regulation.
- rs769446 genotype does not appear to affect plasma lipoprotein levels in healthy APOE ε3/ε3 individuals.
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