Apolipoprotein E (APOE) transports fat-soluble vitamins and cholesterol into the lymph system and then into the blood. APOE has been shown to reduce cholesterol levels, reduce the risk of heart disease, and reduce inflammation [R][R][R].
There are at least three slightly different versions (alleles) of the APOE gene. The major alleles are called e2, e3, and e4. The most common allele is e3, which is found in more than half of the general population.
Certain APOE varieties may lead to increased risk of heart disease, high cholesterol, inflammation, depression and cancer [R]. In particular, the APOE4 variety cannot accomplish the beneficial functions as well that the other varieties can do. People with two APOE4 alleles are 20X more likely to get Alzheimer's.
- Low APOE results in higher cholesterol.
- Low APOE causes increased oxidative stress, inflammation.
- Low APOE is most notably a causal factor in Alzheimer’s.
- Cholesterol levels: APOE participates in cholesterol redistribution from cells with excess cholesterol to those requiring it, thus reducing cholesterol levels [R].
- Prevents Atherosclerosis (cardiovascular disease): In a study done on mice that were missing the APOE gene, it was showed that people with APOE4 had a higher risk of getting atherosclerosis, a disease where plaque is built up in the arteries [R].
- Inflammation: APOE reduces the risk to develop age-related macular degeneration and inflammation [R].
- Sleep disturbances (snoring, sleep apnea): APOE decreased problems in snoring and sleep apnea (in adults without dementia) [R].
- Alzheimer’s: APOE2 can serve a protective role in fighting against Alzheimer’s [R], while th APOE4 variant is a large risk factor for late-onset Alzheimer’s Disease [R].
- Weight Management: APOE3 more efficiently harvests dietary energy and deposits fat in fat tissue compared to APOE4 [R].
- Fatigue: APOE4 gene is associated with fatigue in people who had minor brain injuries [R].
- Depression: High APOE4 levels lead to depression in people with Alzheimer’s Disease [R].
- Migraines: APOE4 was positively linked to headaches [R].
- Brain Hemorrhages: APOE interacts with lipid levels in the brain to play a role in causing brain hemorrhages [R].
- Cancer (renal cell carcinoma and colon adenocarcinoma): Interactions between APOE and other genes are related to higher cancer susceptibility [R].
APOE gene variants have also been studied as a potential risk factor for age-related macular degeneration, an eye disease that is a leading cause of vision loss among older people worldwide. Some studies have suggested that having at least one copy of the APOE e4 allele may help protect against this disease or delay the onset of vision loss, while having at least one copy of the APOE e2 allele may increase the risk of this disease or cause symptoms to appear earlier.
It's better to have this gene increased most of the time.
- RS1065853 (APOE) ??
- RS405509 (APOE) ??
- RS429358 (APOE) ??
- RS438811 (APOE) ??
- RS439401 (APOE) ??
- RS440446 (APOE) ??
- RS445925 (APOE) ??
- RS449647 (APOE) ??
- RS7412 (APOE) ??
- RS769449 (APOE) ??
- RS769452 (APOE) ??
- RS769455 (APOE) ??
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Top Gene-Substance Interactions
Gene Interacts with Diseases
|Disease||Inference Score||References/Inference chemicals|
If you have an APOE variety that doesn't work as well (APOE4), you can do a number of thngs to increase its production or function. You should be promotin the following:
- Education: More years of education meant higher levels of APOE [R].
- Mental Exercises: Daily mental exercises (puzzles, reading, etc.) help stabilize APOE levels and prevent the decline of brain function [R].
- Low Fat Diet [R].
- Lowering cholesterol [R]- lowering serum cholesterol levels may reduce a person’s risk for Alzheimer’s disease, even if they have two ApoE4 alleles, thus reducing the risk from nine or ten times the odds of getting Alzheimer's down to just two times the odds.
- Cold Showers
- Fish oil/DHA
- Vitamin A/Retinol
APOE is decreased by inflammation, but increased by TGF-beta.
All Ways to Increase Gene
|Arsenic||Increases response to substance||Humans (R)||Substances of Biological Interest, Airborne Pollutant, Cigarette Toxin, Food Toxin, Household Toxin, Natural Toxin, Pesticide, Pollutant|
|Arachidonic Acid||Increases abundance, Increases reaction||Humans (R) , Humans (R)||Substances of Biological Interest, Important Natural Compounds|
|Phytosterols||Increases expression||Mice (R)||Consumable Natural Treatments, Substances of Biological Interest, Beneficial Substances, Important Natural Compounds|
|Dazoxiben||Increases abundance, Increases reaction||Humans (R) , Humans (R)||Substances of Biological Interest|
|11-dehydro-thromboxane B2||Increases abundance, Increases reaction||Humans (R) , Humans (R)||Obscure Chemicals|
|Tempol||Increases abundance, Increases reaction||Humans (R) , Humans (R)||Consumable Natural Treatments, Substances of Biological Interest, Beneficial Substances, Important Natural Compounds|
|Tetrachlorodibenzodioxin||Increases expression||Humans (RR)||Substances of Biological Interest, Airborne Pollutant, Industrial/Workplace Toxin, Pollutant, Synthetic Toxin|
|Diethylhexyl Phthalate||Increases response to substance||Mice (R)||Substances of Biological Interest, Airborne Pollutant, Food Toxin, Household Toxin, Industrial/Workplace Toxin, Pesticide, Pollutant, Synthetic Toxin|
|Penicillins||Increases expression||Rats (R)||Substances of Biological Interest|
|Tosylphenylalanyl Chloromethyl Ketone||Increases expression, Increases reaction||Humans (R) , Humans (R)||Substances of Biological Interest|
All Ways to Decrease Gene
|Dietary Fats||Decreases expression||Hamsters (R)||Consumable Natural Treatments, Substances of Biological Interest, Beneficial Substances, Important Natural Compounds|
|Cholesterol, Dietary||Decreases expression||Hamsters (R)|
|Notoginsenoside R1||Decreases abundance, Decreases reaction||Mice (R) , Mice (R)|
|Felodipine||Decreases reaction||Mice (R)||Substances of Biological Interest|
|Fexofenadine||Decreases expression, Decreases reaction||Mice (R) , Mice (R)||Substances of Biological Interest|
|Gentamicin C||Decreases activity, Decreases expression , Decreases reaction||Boars (R) , Boars (R) , Boars (R)||Popular drugs, Substances of Biological Interest|
|Cetirizine||Decreases expression, Decreases reaction||Mice (R) , Mice (R)||Drug, Substances of Biological Interest, Food Toxin, Synthetic Toxin|
|Myricitrin||Decreases activity, Decreases reaction||Mice (R) , Mice (R)||Substances of Biological Interest, Beneficial Substances, Important Natural Compounds|
|Streptozocin||Decreases reaction||Mice (R)||Drug, Substances of Biological Interest, Synthetic Toxin|
|Nimesulide||Decreases expression, Decreases reaction||Mice (R) , Mice (R)||Drug, Substances of Biological Interest|
Conditions with Increased Gene Activity
|Condition||Change (log2fold)||Comparison||Species||Experimental variables||Experiment name|
Conditions with Decreased Gene Activity
|Condition||Change (log2fold)||Comparison||Species||Experimental variables||Experiment name|
The following transcription factors increase gene production (R):
Occurs in all lipoprotein fractions in plasma. It constitutes 10-20% of very low density lipoproteins (VLDL) and 1-2% of high density lipoproteins (HDL). APOE is produced in most organs. Significant quantities are produced in liver, brain, spleen, lung, adrenal, ovary, kidney and muscle.
- Antioxidant Activity
- Beta-Amyloid Binding
- Cholesterol Binding
- Cholesterol Transporter Activity
- Heparin Binding
- Identical Protein Binding
- Lipid Binding
- Lipid Transporter Activity
- Lipoprotein Particle Binding
- Low-Density Lipoprotein Particle Receptor Binding
- Metal Chelating Activity
- Phosphatidylcholine-Sterol O-Acyltransferase Activator Activity
- Phospholipid Binding
- Protein Homodimerization Activity
- Tau Protein Binding
- Very-Low-Density Lipoprotein Particle Receptor Binding
- Ampa Glutamate Receptor Clustering
- Artery Morphogenesis
- Cellular Calcium Ion Homeostasis
- Cgmp-Mediated Signaling
- Cholesterol Catabolic Process
- Cholesterol Efflux
- Cholesterol Homeostasis
- Cholesterol Metabolic Process
- Chylomicron Remnant Clearance
- Cytoskeleton Organization
- Fatty Acid Homeostasis
- G-Protein Coupled Receptor Signaling Pathway
- High-Density Lipoprotein Particle Assembly
- High-Density Lipoprotein Particle Clearance
- High-Density Lipoprotein Particle Remodeling
- Intracellular Transport
- Lipoprotein Biosynthetic Process
- Lipoprotein Catabolic Process
- Lipoprotein Metabolic Process
- Long-Chain Fatty Acid Transport
- Low-Density Lipoprotein Particle Remodeling
- Maintenance Of Location In Cell
- Negative Regulation Of Beta-Amyloid Formation
- Negative Regulation Of Blood Coagulation
- Negative Regulation Of Blood Vessel Endothelial Cell Migration
- Negative Regulation Of Canonical Wnt Signaling Pathway
- Negative Regulation Of Cholesterol Biosynthetic Process
- Negative Regulation Of Cholesterol Efflux
- Negative Regulation Of Dendritic Spine Development
- Negative Regulation Of Dendritic Spine Maintenance
- Negative Regulation Of Endothelial Cell Proliferation
- Negative Regulation Of Inflammatory Response
- Negative Regulation Of Lipid Biosynthetic Process
- Negative Regulation Of Lipid Transport Across Blood Brain Barrier
- Negative Regulation Of Map Kinase Activity
- Negative Regulation Of Neuron Apoptotic Process
- Negative Regulation Of Neuron Death
- Negative Regulation Of Phospholipid Efflux
- Negative Regulation Of Platelet Activation
- Negative Regulation Of Postsynaptic Membrane Organization
- Negative Regulation Of Presynaptic Membrane Organization
- Neuron Projection Regeneration
- Nitric Oxide Mediated Signal Transduction
- Nmda Glutamate Receptor Clustering
- Phospholipid Efflux
- Positive Regulation By Host Of Viral Process
- Positive Regulation Of Beta-Amyloid Formation
- Positive Regulation Of Cgmp Biosynthetic Process
- Positive Regulation Of Cholesterol Efflux
- Positive Regulation Of Cholesterol Esterification
- Positive Regulation Of Dendritic Spine Development
- Positive Regulation Of Dendritic Spine Maintenance
- Positive Regulation Of Lipid Biosynthetic Process
- Positive Regulation Of Lipid Transport Across Blood Brain Barrier
- Positive Regulation Of Low-Density Lipoprotein Particle Receptor Catabolic Process
- Positive Regulation Of Membrane Protein Ectodomain Proteolysis
- Positive Regulation Of Neurofibrillary Tangle Assembly
- Positive Regulation Of Neuron Death
- Positive Regulation Of Nitric-Oxide Synthase Activity
- Positive Regulation Of Phospholipid Efflux
- Positive Regulation Of Postsynaptic Membrane Organization
- Positive Regulation Of Presynaptic Membrane Organization
- Protein Import
- Receptor-Mediated Endocytosis
- Regulation Of Axon Extension
- Regulation Of Beta-Amyloid Clearance
- Regulation Of Cdc42 Protein Signal Transduction
- Regulation Of Gene Expression
- Regulation Of Neuron Death
- Regulation Of Neuronal Synaptic Plasticity
- Regulation Of Tau-Protein Kinase Activity
- Response To Dietary Excess
- Response To Reactive Oxygen Species
- Retinoid Metabolic Process
- Reverse Cholesterol Transport
- Synaptic Transmission, Cholinergic
- Triglyceride Catabolic Process
- Triglyceride Metabolic Process
- Very-Low-Density Lipoprotein Particle Clearance
- Very-Low-Density Lipoprotein Particle Remodeling
- Virion Assembly
- Human Serum Albumin
- Serum Albumin Iodonated