Genetic variant in 30% of Europeans that protects against Alzheimer's

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petri.d
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Genetic variant in 30% of Europeans that protects against Alzheimer's

Post by petri.d »

Last December Emmanuel Mignot's lab at Stanford University published a pre-print showing that a genetic variant common among people of European descent protects against Alzheimer's (link to pre-print: https://www.medrxiv.org/content/10.1101 ... 21268354v1).

While several genetic variants that protect against Alzheimer's have recently been reported, I thought this one was interesting because it was so common - 30% of people of European descent should have the protective variant. Also, the variant is in a group of genes that presents antigens to the immune system. Thus, people with this protective variant (HLA-DRB1*04) may be naturally vaccinating themselves against Tau tangles (or might be good candidates for vaccination with Tau peptides).

I looked to see if I had the variant and unfortunately I don't. But I thought I'd share how I determined I don't have the variant in case others wanted to look.

There are a couple of ways to determine if you have the protective HLA-DRB1 allele. First, you could PCR amplify the corresponding DNA from a saliva sample and have it sequenced. This method is cheap and quick, but you need access to a lab or someone willing to do it.

Another method is to have your genome sequenced. You can do this for ~$300 through Nebula Genomics (https://nebula.org/whole-genome-sequencing-dna-test/). It takes ~6 months to get your full sequence.

When you get your sequence you just look up HLA-DRB1 in the genome browser. You have to reverse the sequence and translate it. When that's done, just count over 13 amino acids (going right to left) and determine if you have a histidine residue (H). Then go another 20 residues (right to left, position 33) and also determine if you have an H. If you have an H at both 13 and 33 then you have the protective allele! If not, you may still have other protective variants, just not this specific one.

I have 13P and 33R. My HLA-DRB1 subtype is 15, not 04, which is protective. Below is an image of my results. If anyone wants to determine if they carry the protective allele and needs help just send me a message.
Genome_Browser_-_Nebula_Genomics.jpg
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Brian4
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Re: Genetic variant in 30% of Europeans that protects against Alzheimer's

Post by Brian4 »

Thanks Petri.

For those who don't know, to reverse and translate, click on the gear icons to the right in the genome browser.

Brian
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J11
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Re: Genetic variant in 30% of Europeans that protects against Alzheimer's

Post by J11 »

DRB 1.png
I want to double check my result. It appears to be the same as yours.
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Brian4
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Re: Genetic variant in 30% of Europeans that protects against Alzheimer's

Post by Brian4 »

Mine was also the same as yall's, by the way. Oh well.
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J11
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Re: Genetic variant in 30% of Europeans that protects against Alzheimer's

Post by J11 »

By the way, does Nebula post mitochondrial DNA results? Looks like the drop down does include M.
This is frustrating because a few days ago I came across a mitochondrial AD genotype, though I might now have trouble finding it again.

Here it is. Recently reported on the Science forum. SHMOOSE mitochondrial SNP rs2853499 G12372A
https://www.nature.com/articles/s41380-022-01769-3
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Re: Genetic variant in 30% of Europeans that protects against Alzheimer's

Post by Plumster »

Is this the same haplotype that causes biotoxin sensitivity, the so-called "dreaded" and "worst" haplotype if you are exposed to mycotoxins, which I have been on and off for a decade? I do have DRB1*04:01:01G, according to my labs. If it is the same one, I'm glad to see some benefits from it, though perhaps my previous mold exposure cancels it out!

It looks like Labcorp can provide the HLA test:
https://www.labcorp.com/tests/167120/hl ... resolution
e3/4 MTHFR C677T/A1298C COMT V158M++ COMT H62H++ MTRR A66G ++ HLA DR
treman123
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Re: Genetic variant in 30% of Europeans that protects against Alzheimer's

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Does anyone know if this information (the “30% of Europeans“ protective gene/allele) is available if 23 and me or ancestry DNA has been done?
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Re: Genetic variant in 30% of Europeans that protects against Alzheimer's

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treman123 wrote: Sat Oct 08, 2022 4:49 pm Does anyone know if this information (the “30% of Europeans“ protective gene/allele) is available if 23 and me or ancestry DNA has been done?
As far as I know, it is not in 23andme.
e3/4 MTHFR C677T/A1298C COMT V158M++ COMT H62H++ MTRR A66G ++ HLA DR
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