APOE

The apolipoprotein E (ApoE) gene makes a protein which, which 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 variants of ApoE, known as ApoE2, ApoE3, and ApoE4. Note that each of these types can actually have additional changes too, so there are different subtypes as well. The most common form overall is the "standard" ApoE3, and therefore more people inherited one ApoE3 from each parent than any other of the possible pairs of variants.

Promethease uses:

• gs189 ApoE1 allele = rs429358(C) + rs7412(T) = the rare missing allele
• gs186 ApoE2 allele = rs429358(T) + rs7412(T)
• gs187 ApoE3 allele = rs429358(T) + rs7412(C) = the most common
• gs188 ApoE4 allele = rs429358(C) + rs7412(C) = increased Alzeheimer's risk
• gs216 ApoE4/E4 allele = rs429358(C;C) + rs7412(C;C) = very increased Alzeheimer's risk

Patients with Alzheimer's disease who have at least one ApoE4 allele were found to benefit from a therapy that was ineffective in those who lacked ApoE4 [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 ApoE4 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 ApoE3/ApoE3 carriers.

[2] uses old allele format

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]

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 ApoE2 and ApoE4 carriers compared with ApoE3 homozygotes.[PMID 18494374]

abstract ApoE4 and herpes simplex virus type 1 appear related to the development of Alzheimer's disease.