Apolipoprotein E Polymorphism and Cardiovascular Risk Factors

Apolipoprotein E (APOE) is a key determinant of lipoprotein handling, with three primary alleles denoted ε2, ε3 and ε4. These alleles alter receptor binding and hepatic clearance of triglyceride-rich lipoproteins, thereby shaping plasma cholesterol and triglyceride profiles. Carriers of the ε4 allele typically exhibit higher low-density lipoprotein cholesterol (LDL-C) and lower high-density lipoprotein cholesterol (HDL-C) compared with ε3 homozygotes, contributing to an elevated risk of coronary artery disease and ischaemic stroke. By contrast, ε2 carriers often display reduced LDL-C but may present with hypertriglyceridaemia in certain contexts. Beyond lipid modulation, APOE variants influence vascular inflammation, macrophage phenotype, endothelial function and plaque stability. Interactions between APOE genotype and traditional risk factors—such as hypertension, diabetes and smoking—further modify individual susceptibility to atherosclerosis and its clinical sequelae. Population studies reveal variation in allele frequencies across ethnic groups, underscoring the global relevance of APOE genotype in cardiovascular epidemiology. Translational research exploring targeted interventions, from genotype-driven lipid-lowering strategies to modulation of lipoprotein receptors, heralds personalised approaches to cardiovascular prevention. Recent advances in understanding APOE-mediated mechanisms of vascular injury offer opportunities to refine risk stratification and to develop novel therapies that address both lipid and inflammatory pathways. The breadth of APOE research spans molecular biology, clinical trials and public health, reflecting its central role in cardiovascular risk assessment and management.

Research from Nature Portfolio

A recent study applied competing-risk models to characterise how the ε4 allele influences mortality in older adults. It reveals that APOE4 carriers face increased risk of death when high Alzheimer-type neuropathology is observed at autopsy, whereas they show a relative survival benefit in its absence. This duality emphasises the allele’s pleiotropic effects on vascular and neurodegenerative processes and suggests that cardiovascular health modulates cognitive ageing in ε4 carriers, pointing towards integrated strategies addressing both lipid and inflammatory mechanisms to improve survival outcomes.

Apolipoprotein E Polymorphism and Cardiovascular Risk Factors publication trend

The graph below shows the total number of articles in apolipoprotein e polymorphism and cardiovascular risk factors across all publications each year (not limited to Nature Index journals).

Technical terms

Apolipoprotein E (APOE): Glycoprotein that regulates lipid transport and clearance with three common alleles (ε2, ε3, ε4).

Polymorphism: Occurrence of two or more genetic variants at a locus within a population.

Dyslipidaemia: Abnormal plasma lipid concentrations linking to cardiovascular pathology.

Atherosclerosis: Progressive arterial disease characterised by lipid deposition and inflammatory cell infiltration.

Genotype: The specific allele combination an individual carries at a gene locus.

References

1. Lower mortality risk in APOE4 carriers with normal cognitive ageing. Scientific Reports (2023).
2. APOE Gene Variation’s Impact on Cardiovascular Health: A Case-Control Study. Biomedicines (2024).
3. The independent association between 25 (OH) vitamin D deficiency, HOMA-IR, and lipid profile with APOE genotyping in obese cases with and without T2DM. Diabetology & Metabolic Syndrome (2024).
4. Apolipoprotein E gene polymorphism: effects on plasma lipids and risk of type 2 diabetes and coronary artery disease. Cardiovascular Diabetology (2012).
5. Modulation of plasma triglyceride levels by apoE phenotype: a meta-analysis.. Journal of Lipid Research (1992).
6. Apolipoprotein E4 Impairs Macrophage Efferocytosis and Potentiates Apoptosis by Accelerating Endoplasmic Reticulum Stress*. Journal of Biological Chemistry (2012).
7. Association of APOE gene polymorphism with lipid profile and coronary artery disease in Afro-Caribbeans. PLOS ONE (2017).