How to Read Test Results of Apoe4

Nosotros're writing this blog to address a relatively common question we get most a protein known as apolipoprotein E (ApoE) and how people can go conflicting results about some key variants in the APOE gene when comparison their 23andMe wellness report, with that from other sites.

What is ApoE?

ApoE)is a poly peptide that is involved in the metabolism of fats, and when combined with fatty, forms a very-low-density lipoprotein (VLDL). For this reason there is a lot of interest around APOE and cardiovascular health. But APOE is perhaps more famous because of a potent correlation between certain polymorphisms and an increased risk of developing Alzheimer's disease (AD) in older age.

For more on ApoE4, consider checking out our case study podcast on how ultramarathon runner Gerald Holbrook changed his diet to business relationship for his ApoE condition.

ApoE4 does NOT guarantee Alzheimer's disease

Before we go farther I actually want to focus on the "increased gamble" highlighted in bold. Carrying the SNPs with this associated riskDOES NOT mean you lot will develop AD, it only means that your run a risk is increased.

There are many other risk factors out in that location (smoking, obesity etc), only ApoE status gets a lot of involvement as it's easy to test for and oftentimes seems scarier equally it's non a factor that can be easily mitigated (for example past giving up smoking).

These ApoE variants are thought to increase the chance of developing AD by increasing the assemblage of Amyloid β protein, a hallmark of the disease, although this hasn't been confirmed and other potential mechanisms exist. ⁱ

What are the ApoE variants and what do they mean?

Here'southward where it gets somewhat confusing. There are three common alleles for theAPOE gene.  Apo-ε2, ε3 and ε4 (often called E2 etc…). There are also some less common versions such every bit ε1 and even an ε5 allele. You may read that these forms just don't exist, that is incorrect they are just rare.

For now allow's focus on ε2 to ε4. Every bit you know, we acquit two copies of almost every factor in the body. That ways that y'all tin can take one copy of ε2 and 1 of ε4, or two of ε4 and so on. Knowing which two copies you have is of import equally from this you can infer your AD risk.

I've summarized the various risks in the table beneath which are adapted from this paper. ²

APOE Allele 1	APOE Allele 2	AD Risk
ε2	ε2	0.8
ε2	ε3	0.8
ε2	ε4	one.4
ε3	ε3	Neutral one
ε3	ε4	1.4
ε4	ε4	iii.9

So from the above yous can come across that carrying ii copies of ε4 significantly increases your risk of developing Ad. There are several studies that have looked at this and then yous may often see different numbers, merely the pattern is the same.

Again, increased take a chance is NOT guaranteed Alzheimer'due south disease. If annihilation, learning you bear an ApoE4 variant is a signal that watching what you eat, blood pressure, practice, and what your blood lipid markers wait like is all that much more than necessary.

So how do I make up one's mind what ApoE variants I accept?

The all-time and most authentic way to determine this is to sequence your APOE gene which will give you the most accurate readout. But this isn't feasible for near people, and then the next all-time way is to apply your raw information from a consumer genotyping service such as 23andMe or ancestry.com.

And this is where it gets really interesting. If we focus on the most common three variants again there are two SNPs we're interested in, rs429358 and rs7412. I've summarised these in the table below.

rs429358	Allele
T	ε2
T	ε3
C	ε4

If you await at that table you lot tin see that the "C" allele of rs429358 is a good marker for ε4, whereas "T" could be either ε2 or ε3. Importantly this is the only SNP that 23andMe use to determine your ApoE status in their health report. Let's expand that table and meet if there may be a ameliorate approach.

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

Equally you can run across past adding in the rs7412 SNP we can now differentiate between ε2 and ε3 forms, and you lot tin as well run into that rs429358-C and rs7412-C gives us ε4. But what near rs429358-C and rs7412-T? Well in the table above you tin can see that this actually gives us the ε1 form of ApoE.

The lesser line

In sum, and due to FDA regulation, 23andme simply reports on i of the relevant SNPs for determining ApoE4 status. This leaves open the possibility that someone could be listed equally a 3/4 in 23andme and actually carry two copies of ApoE4.

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Source: https://www.mygenefood.com/blog/23andme-and-apoe4-reporting-how-to-interpret-your-results/

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