APOE

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Full nameapolipoprotein E
EntrezGene348
PheGenI348
VariationViewer348
ClinVarAPOE
dbSNP348
SADR348
HugeNav348
wikipediaAPOE
googleAPOE
gopubmedAPOE
EVSAPOE
HEFalMpAPOE
23andMeAPOE
UniProtP02649
EnsemblENSG00000130203
OMIM107741
EVSAPOE
# SNPs36
 Max MagnitudeChromosome positionSummary
Rs11083750044,908,601
Rs121918392044,907,777
Rs121918393044,908,756
Rs121918394044,908,786
Rs121918395044,909,032
Rs121918396044,908,979
Rs121918397044,908,784
Rs121918398044,909,171
Rs121918399044,907,843
Rs12982192044,908,002
Rs140808909044,909,080
Rs190853081044,909,083
Rs1997680052.144,909,057
Rs201672011044,907,807
Rs267606661044,909,101
Rs267606662044,908,804
Rs267606663044,909,021
Rs267606664044,908,730
Rs28931576044,907,894
Rs28931577044,908,645
Rs28931578044,908,751
Rs28931579044,909,236
Rs387906567044,908,774
Rs387906568044,909,020
Rs397514253044,908,531
Rs397514254044,908,731
Rs40550944,905,579
Rs4293581.244,908,684
Rs43940144,911,194
Rs440446044,905,910
Rs44964744,905,307
Rs7412044,908,822
Rs769446044,905,371
Rs769449044,906,745
Rs769452044,907,853
Rs769455044,908,783
The apolipoprotein E (ApoE) gene makes a protein which, when combined with fat, becomes a lipoprotein. The lipoprotein ApoE is a very low-density lipoprotein, responsible in part for removing cholesterol from the bloodstream. Variations in ApoE affect cholesterol metabolism, which in turn alter your chances of having heart disease and in particular a heart attack or a stroke. Variations in ApoE are also associated with altered odds of having Alzheimer's disease and other diseases.

There are three relatively common allelic variants of ApoE, as defined by two SNPs, rs429358 and rs7412 known as ApoE-ε2, ApoE-ε3, and ApoE-ε4. The proteins produced by these genes are called ApoE2, ApoE3, and ApoE4. The most common variant overall is the "standard" ApoE-ε3, and therefore more people inherited one ApoE-ε3 from each parent than any other of the possible pairs of variants. Note that each of these types can actually have additional changes too, so there are different subtypes as well.

Promethease uses:

  • Apo-ε1/ε1 gs267 rs429358(C;C) rs7412(T;T) the rare missing allele
  • Apo-ε1/ε2 gs271 (C;T) (T;T)
  • Apo-ε1/ε3 gs270 (C;T) (C;T) ambiguous with ε2/ε4
  • Apo-ε1/ε4 gs272 (C;C) (C;T)
  • Apo-ε2/ε2 gs268 (T;T) (T;T)
  • Apo-ε2/ε3 gs269 (T;T) (C;T)
  • Apo-ε2/ε4 gs270 (C;T) (C;T) ambiguous with ε1/ε3
  • Apo-ε3/ε3 gs246 (T;T) (C;C) the most common
  • Apo-ε3/ε4 gs141 (C;T) (C;C)
  • Apo-ε4/ε4 gs216 (C;C) (C;C) ~11x increased Alzheimer's risk

Allele specific genosets gs189, gs186, gs187 and gs188 were previously used, but have now been replaced by the genotype specific ones shown above.


Patients with Alzheimer's disease who have at least one ApoE-ε4 allele were found to benefit from a therapy that was ineffective in those who lacked ApoE-ε4 [1]


Note: Although ApoE status is technically defined by these two SNPs, rs429358 and rs7412, a SNP in the adjacent ApoC1 gene, rs4420638, is co-inherited with ApoE and thus predictive of it, as published in the following report:

  • [PMID 17192785] The researchers found that on testing DNA samples from 1,086 well-characterized Alzheimer's disease cases, a single SNP (rs4420638) lying 14 kb distal to the ApoE locus has a powerful association with late-onset AD (corrected p value was 5.3 x 10 e-34). No other SNP showed as robust an association. The authors estimated that people with two ApoE-ε4 copies (i.e. presumably indicated by having either the rs4420638(G;G) or rs429358(C;C) genotypes) have a 25-fold increased risk for developing the disease compared to Apo-ε3/Apo-ε3 carriers.

[2] uses old allele format

Apo-ε4 carriers may have their risk of developing Alzheimer's disease modified by SNPs elsewhere in their genomes. For example:

  • rs2373115, a SNP in the GAB2 gene
  • Inheritance of the rs1799724(T) allele appears to synergistically increase the risk of Alzheimer's in ApoE-ε4 carriers and is associated with altered CSF Abeta42 levels [PMID 15895461]
  • A haplotype of 3 SNPs in the POLD1 gene; the combined presence of this POLD1 I-G-T haplotype and the ApoE-ε4 allele almost doubles the risk of AD (odds ratio: 10.09, CI: 3.88-26.25, =<0.0001) compared to ApoE-ε4 carriers alone.[PMID 17498878]


A study of 2,000+ individuals living in Costa Rica found a gene-diet interaction involving the ApoE alleles. Specifically, high fat diets cause a greater LDL cholesterol response and higher heart attack risk in ApoE-ε2 and ApoE-ε4 carriers compared with ApoE-ε3 homozygotes.[PMID 18494374]

abstract ApoE-ε4 and herpes simplex virus type 1 appear related to the development of Alzheimer's disease.