The presence of both rs7412(C;C) and rs429358(C;C) indicates the highest risk ApoE4/ApoE4. This is checked for by gs216.
gs188, gs141, gs143 and other genosets also use this snp pair.
More information about ApoE4 is well explained at this blog post.
ApoE4 is notable as being the variation that James Watson requested not to learn when having his genome sequenced. User:Steven Pinker also requested that ApoE information be removed from his PGP10 data. In this way it has become a useful reference point when talking about genetic information that some people do not desire to learn. It is used as a reference point in the magnitude scale used within SNPedia.
It has been associated for over 20 years in a dose-dependent manner with increased total and LDL-cholesterol levels, and thus increased risk for heart disease and myocardial infarctions. [PMID 3698268]
Inheritance of the rs1799724(T) allele appears to synergistically increase the risk of Alzheimer's in APOE4 carriers and is associated with altered CSF Abeta42 levels [PMID 15895461]
[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 ApoE4 copies have a 25-fold increased risk for developing the disease compared to ApoE3/ApoE3 carriers. [1]
ApoE4 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 ApoE4 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 ApoE4 allele almost doubles the risk of AD (odds ratio: 10.09, CI: 3.88-26.25, =<0.0001) compared to ApoE4 carriers alone.[PMID 17498878]
- rs638405, a SNP in the BACE1 gene
The original patents covering the utility of ApoE4 genotyping to predict Alzheimer's disease have been (controversially) exclusively licensed by Duke University to Athena Diagnostics; these include patent nos. 5,508,167 (issued April 16, 1996, implying expiration April 16, 2013), 5,716,828 (issued Feb. 10, 1998), and 6,027,896 (issued Feb. 22, 2000).
