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APOE

From SNPedia
(Redirected from ApoE)
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Full nameapolipoprotein E
EntrezGene348
PheGenI348
VariationViewer348
ClinVarAPOE
GeneCardsAPOE
dbSNP348
DiseasesAPOE
SADR348
HugeNav348
wikipediaAPOE
googleAPOE
gopubmedAPOE
EVSAPOE
HEFalMpAPOE
MyGene2APOE
23andMeAPOE
UniProtP02649
EnsemblENSG00000130203
OMIM107741
# SNPs44
 Max MagnitudeChromosome positionSummary
i500021745,412,031
i6007504
i6007510
i6007512
rs11083750044,908,601
rs121918392044,907,777
rs121918393644,908,756
rs121918394544,908,786
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
rs200703101044,908,757
rs201672011044,907,807
rs267606661044,909,101
rs267606662044,908,804
rs267606663044,909,021
rs267606664444,908,730
rs28931576044,907,894
rs28931577044,908,645
rs28931578044,908,751
rs28931579044,909,236
rs387906567344,908,774
rs387906568044,909,020
rs397514253044,908,531
rs397514254044,908,731
rs405509044,905,579
rs4293581.244,908,684
rs439401044,911,194
rs440446044,905,910
rs449647244,905,307
rs515726148044,908,796
rs527236160044,908,587
rs7412144,908,822
rs769446044,905,371
rs769449044,906,745
rs769450044,907,187
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.


rs429358 rs7412 Name
C T ε1
T T ε2
T C ε3
C C ε4


Common name Genoset Magnitude rs429358 rs7412 Comment
Apo-ε1/ε1 gs267 6 (C;C) (T;T) the rare missing allele
Apo-ε1/ε2 gs271 2.5 (C;T) (T;T)
Apo-ε1/ε3 gs270 2.6 (C;T) (C;T) ambiguous ε2/ε4 or ε1/ε3
Apo-ε2/ε4 gs270 2.6 (C;T) (C;T) ambiguous ε2/ε4 or ε1/ε3
Apo-ε1/ε4 gs272 2.5 (C;C) (C;T)
Apo-ε2/ε2 gs268 4 (T;T) (T;T) good; lowest risk
Apo-ε2/ε3 gs269 2 (T;T) (C;T)
Apo-ε3/ε3 gs246 2 (T;T) (C;C) the most common
Apo-ε3/ε4 gs141 3 (C;T) (C;C)
Apo-ε4/ε4 gs216 6 (C;C) (C;C) ~11x increased Alzheimer's risk


The 'missing allele' ApoE1 is visible on the top strand. The bottom strand shows an ApoE3
The top strand is an ApoE2. The bottom strand is an ApoE4

Allele specific genosets gs189 and gs188 were previously used, but have now been replaced by the genotype specific ones shown above.

Word of caution to those with data from Ancestry.com: in our experience, based on data in OpenSNP and from Promethease users since 2006, Ancestry data always reports rs429358 as (T;T), even for people who's data from other sources indicates they are (C;T). Therefore, until Ancestry corrects this false negative problem, be aware that the ApoE genosets defined by the genotypes listed above (and therefore assigned by Promethease) will be inaccurate if they are based on (inaccurate) Ancestry data. Specifically, some percentage of Ancestry users who are supposedly gs246 positive (Apo-ε3/ε3) are actually either gs141 (Apo-ε3/ε4) or gs216 (Apo-ε4/ε4).

A rare form of the ApoE3 allele, rs121918393, also known as the Christchurch (R136S) mutation, appears to convey a significant amount of resistance to PSEN1-based form of autosomal dominant Alzheimer’s, according to a 2019 study.[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.


APOE-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.