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
Rs1108375044,908,601
Rs12191839244,907,777
Rs12191839344,908,756
Rs12191839444,908,786
Rs12191839544,909,032
Rs12191839644,908,979
Rs12191839744,908,784
Rs12191839844,909,171
Rs12191839944,907,843
Rs1298219244,908,002
Rs14080890944,909,080
Rs19085308144,909,083
Rs19976800544,909,057
Rs20167201144,907,807
Rs26760666144,909,101
Rs26760666244,908,804
Rs26760666344,909,021
Rs26760666444,908,730
Rs2893157644,907,894
Rs2893157744,908,645
Rs2893157844,908,751
Rs2893157944,909,236
Rs38790656744,908,774
Rs38790656844,909,020
Rs39751425344,908,531
Rs39751425444,908,731
Rs40550944,905,579
Rs42935844,908,684
Rs43940144,911,194
Rs44044644,905,910
Rs44964744,905,307
Rs741244,908,822
Rs76944644,905,371
Rs76944944,906,745
Rs76945244,907,853
Rs76945544,908,783
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.