Information on RS4420638 (A;A)?

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DeterminedActivist
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Information on RS4420638 (A;A)?

Postby DeterminedActivist » Thu Nov 07, 2019 1:59 am

I did Ancestry test, but they have a problem with one of the APOE genoset SNPs, always reporting T;T instead of other possibilities. I am CC for the other, which means I could be E4/E4.

I have seen SNP RS4420638 to be correlated with rs429358 (the Ancestry mishap SNP). What is your status of RS4420638 and what is your status of rs429358?

My rs4420638 is A;A
My rs429358 is unknown because of faulty Ancestry data.

I found the following study which depicts rs4420638 status versus how many E4 alleles a person has. https://www.frontiersin.org/files/Artic ... 0-g004.jpg

Looks like none in AA group have two E4 alleles...

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Re: Information on RS4420638 (A;A)?

Postby NF52 » Thu Nov 07, 2019 8:22 am

DeterminedActivist wrote:I did Ancestry test, but they have a problem with one of the APOE genoset SNPs, always reporting T;T instead of other possibilities. I am CC for the other, which means I could be E4/E4...
My rs4420638 is A;A
My rs429358 is unknown because of faulty Ancestry data....
Looks like none in AA group have two E4 alleles...
Hi Determined Activist!

I hope that you got interesting data from your Ancestry report, and that we can help a little on that darn missing data, a source of consternation to multiple visitors to our forum!
Here's a link to an explanation that is consistent with what you found: https://www.snpedia.com/index.php/Rs4420638 It looks like you have little risk of having ApoE 4/4.
I have ApoE 4/4 and also have the G/G allele on rs3320638; my ApoE 3/3 husband is like you, with an A/A report.

So it sounds like you may be ApoE 3/4, like about 20% of the population with European ancestry. Like my ApoE 3/4 adult children, that means you have time, lifestyle choices and determined activism on your side to manage the 20% or so current risk those genes bring of either mild cognitive impairment or Alzheimer's by age 85.

Here's some evidence for that optimism in the link below: people who maintain a high level of social and cognitive engagement, as you are doing, appear to prevent or delay any cognitive declines by 40% or more:

Can Cognitive and Physical Activity in Midlife Reduce the Risk of Dementia in Later Years? Researchers Say Yes
Last edited by NF52 on Thu Nov 07, 2019 5:35 pm, edited 1 time in total.
4/4 and still an optimist!

DeterminedActivist
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Re: Information on RS4420638 (A;A)?

Postby DeterminedActivist » Thu Nov 07, 2019 10:55 am

NF52 wrote:
DeterminedActivist wrote:I did Ancestry test, but they have a problem with one of the APOE genoset SNPs, always reporting T;T instead of other possibilities. I am CC for the other, which means I could be E4/E4...
My rs4420638 is A;A
My rs429358 is unknown because of faulty Ancestry data....
Looks like none in AA group have two E4 alleles...
Hi Determined Activist!

I hope that you got interesting data from your Ancestry report, and that we can help a little on that darn missing data, a source of consternation to multiple visitors to our forum!
Here's a link to an explanation that is consistent with what you found: https://www.snpedia.com/index.php/Rs4420638 It looks like you have little risk of having ApoE 4/4.
I have ApoE 4/4 and also have the G/G allele on rs3320638; my ApoE 3/3 husband is like you, with a G/G report.

So it sounds like you may be ApoE 3/4, like about 20% of the population with European ancestry. Like my ApoE 3/4 adult children, that means you have time, lifestyle choices and determined activism on your side to manage the 20% or so current risk those genes bring of either mild cognitive impairment or Alzheimer's by age 85.

Here's some evidence for that optimism in the link below: people who maintain a high level of social and cognitive engagement, as you are doing, appear to prevent or delay any cognitive declines by 40% or more:

Can Cognitive and Physical Activity in Midlife Reduce the Risk of Dementia in Later Years? Researchers Say Yes


Honestly, I do not think Ancestry report via Promethease is completely accurate. I have longevity genes and they claim insulin sensitivity yet I have to be on Keto because of insulin resistance. Or sprinter genes when I am not one.

You mean, your husband is A;A not G;G? The picture I provided shows that all A;A have either zero or one E4 allele. So, there is small possibility that I have one E4.

My problem is: I was diagnosed to have high cholesterol on keto diet. I read somewhere that E4 is the reason it goes up and while I am E3/E3 via that proxy SNP most likely, I honestly have doubts. I do not even want to know that exact SNP status to be honest, just like Dr. Watson....

I hope for E3/E3 but my cholesterol response to keto worries me. Are there reasons for my concern? My mother has high cholesterol, as does her father. Could be something else besides one E4 allele.

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Re: Information on RS4420638 (A;A)?

Postby PJD@4411 » Thu Nov 07, 2019 5:33 pm

DeterminedActivist wrote:I did Ancestry test, but they have a problem with one of the APOE genoset SNPs, always reporting T;T instead of other possibilities. I am CC for the other, which means I could be E4/E4.

I have seen SNP RS4420638 to be correlated with rs429358 (the Ancestry mishap SNP). What is your status of RS4420638 and what is your status of rs429358?

My rs4420638 is A;A
My rs429358 is unknown because of faulty Ancestry data.

I found the following study which depicts rs4420638 status versus how many E4 alleles a person has. https://www.frontiersin.org/files/Artic ... 0-g004.jpg

Looks like none in AA group have two E4 alleles...


Hello DeterminedActivist,
Welcome to the forum! We are so happy you have joined this supportive community. We would love the opportunity to get to know you better. Introducing yourself and sharing your story is a great way to get started, it allows you to connect with others.

I see that you have received some feedback regarding Ancestry data and results. You can also find an abundance of information on the Welcome, Primer, and Wikki pages.

Your name DeterminedActivist tells me you have the mindset, will, and courage to conquer!

Again, welcome and please reach out if you have any questions or concerns.
PJ
Think Positive Be Positive
Functional Medicine Certified Health Coach

NF52
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Re: Information on RS4420638 (A;A)?

Postby NF52 » Thu Nov 07, 2019 6:09 pm

DeterminedActivist wrote:...
My rs4420638 is A;A
My rs429358 is unknown because of faulty Ancestry data....
Honestly, I do not think Ancestry report via Promethease is completely accurate. I have longevity genes and they claim insulin sensitivity yet I have to be on Keto because of insulin resistance. Or sprinter genes when I am not one...
My problem is: I was diagnosed to have high cholesterol on keto diet. I read somewhere that E4 is the reason it goes up and while I am E3/E3 via that proxy SNP most likely, I honestly have doubts. I do not even want to know that exact SNP status to be honest, just like Dr. Watson....

I hope for E3/E3 but my cholesterol response to keto worries me. Are there reasons for my concern? My mother has high cholesterol, as does her father. Could be something else besides one E4 allele.
Hi again,

Thank you for catching that mistake; my husband does have A/A on rs4420638, so I used the editing pencil (upper right hand of post) to correct it. I never seem to have typos that leave the meaning intact! I don't see any reason why you need to hunt down that missing SNP to see if you are ApoE 3/4 or 3/3, since you are already committed and engaged in staying healthy. Here's some questions we suggest people consider before testing: Thinking about testing?

As for high cholesterol, that may be from multiple genes without you having to have ApoE4. Here is a helpful link (and quote) from the National Institutes of Health: https://ghr.nlm.nih.gov/condition/hypercholesterolemia#inheritance :
Most cases of high cholesterol are not caused by a single inherited condition, but result from a combination of lifestyle choices and the effects of variations in many genes.

Unless your mother and her father also had early signs of heart disease or stroke before age 55 (for men) or 65 (for women), it's likely that you did not inherit a more serious condition called "familial hypercholesterolemia". I know of someone with that who had a total cholesterol of 300 at age 18; almost everyone on her family died of heart attacks and strokes in their 50's and 60's. She has to aggressively manage that with medication, even though she has never been overweight and is highly active.

It's possible your total cholesterol and LDL score went up if your keto diet was high in animal protein, which contains saturated fat. You may want to check out our wiki resources on Ketosis and the Ketogenic Diet and Cholesterol, Lipids and Treatments, including statins.

Like all activists, celebrate all victories and remember: we're in this for the long haul and we're here for each other during the slumps.
4/4 and still an optimist!

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Re: Information on RS4420638 (A;A)?

Postby DeterminedActivist » Fri Nov 08, 2019 12:25 am

NF52 wrote:Hi again,

Thank you for catching that mistake; my husband does have A/A on rs4420638, so I used the editing pencil (upper right hand of post) to correct it. I never seem to have typos that leave the meaning intact! I don't see any reason why you need to hunt down that missing SNP to see if you are ApoE 3/4 or 3/3, since you are already committed and engaged in staying healthy. Here's some questions we suggest people consider before testing: Thinking about testing?



Is he confirmed E3/E3 though? I could see there is possibility to have one E4 anyways even if A;A for rs4420638 from the picture of the study I posted. Does not seem to be high though. As far as I know, no one has Alzheimers or dementia in my family yet, though I notice my grandfather is a bit slower (he is 85, and has prostate cancer, high blood pressure, cholesterol).

NF52 wrote:As for high cholesterol, that may be from multiple genes without you having to have ApoE4. Here is a helpful link (and quote) from the National Institutes of Health: https://ghr.nlm.nih.gov/condition/hypercholesterolemia#inheritance :
Most cases of high cholesterol are not caused by a single inherited condition, but result from a combination of lifestyle choices and the effects of variations in many genes.

Unless your mother and her father also had early signs of heart disease or stroke before age 55 (for men) or 65 (for women), it's likely that you did not inherit a more serious condition called "familial hypercholesterolemia". I know of someone with that who had a total cholesterol of 300 at age 18; almost everyone on her family died of heart attacks and strokes in their 50's and 60's. She has to aggressively manage that with medication, even though she has never been overweight and is highly active.

It's possible your total cholesterol and LDL score went up if your keto diet was high in animal protein, which contains saturated fat. You may want to check out our wiki resources on Ketosis and the Ketogenic Diet and Cholesterol, Lipids and Treatments, including statins.


My lifestyle is walking most of the week for 30 minutes. I ate a ton of saturated fat from pork so will try to swap it for leaner meats and fish. I had normal cholesterol (4.2) before keto diet but now it is 6.8 at age 26 and was 5.0 (upper limit) on 2018 August. My parents are not old enough yet to see if they have early CVD problems so who knows ... I touch the wood nothing happens but they are NOT proactive of taking care of risk factors. Which frustrates me.

I have read posts on /r/ketogains, /r/keto, /r/ketoscience and most people seem to report their Trigs went down, HDL went up, along with Total and LDL cholesterol, with a good TG/HDL ratio of between 1-2. Mine was above 2 in 2018 August ... I will ask the GP to measure Trigs and I suspect it won't look fine and dandy.

NF52 wrote:Like all activists, celebrate all victories and remember: we're in this for the long haul and we're here for each other during the slumps.


I sometimes feel like spending too much time on this ... and that worry about my health causes me more harm than just eating a hamburger :D

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Re: Information on RS4420638 (A;A)?

Postby NF52 » Fri Nov 08, 2019 6:19 am

DeterminedActivist wrote:...
Is he confirmed E3/E3 though?... As far as I know, no one has Alzheimers or dementia in my family yet, though I notice my grandfather is a bit slower (he is 85, and has prostate cancer, high blood pressure, cholesterol).
My lifestyle is walking most of the week for 30 minutes. I ate a ton of saturated fat from pork so will try to swap it for leaner meats and fish. I had normal cholesterol (4.2) before keto diet but now it is 6.8 at age 26 and was 5.0 (upper limit) on 2018 August. My parents are not old enough yet to see if they have early CVD problems so who knows ... I touch the wood nothing happens but they are NOT proactive of taking care of risk factors. Which frustrates me....
I sometimes feel like spending too much time on this ... and that worry about my health causes me more harm than just eating a hamburger :D
Thanks for sharing more of your story! Sounds like you are in a UK country? My husband and I both have lots of UK ancestry (98% in his 23 & me report!) and loved visiting Ireland, Northern Ireland, Scotland, England, Wales and Jersey. And we've spent more time in Canada than some states!

My husband and I both did 23&me tests in early 2014, and his report was that he was ApoE3/3; mine was ApoE 4/4. My status was confirmed multiple additional times because I volunteered for a clinical prevention trial. The great news for you is that you have what people on the forum sometimes call a N=1 experiment on yourself. You had normal cholesterol, tried a version of a keto diet with lots of pork (considered a "red meat" by the way, so less healthy than chicken, or fish--but yummy!) and at the age of 26 have found that your body isn't able to handle all of that. It looks like your 26 year old total cholesterol of 6.8 mmol/l = 262.95437 mg/dl in US. terms. So it's likely that within 6 months or so you can bring those numbers right back to normal with focusing on less red meat, more whole plant-based foods, including healthy nuts, eggs and fish. (It's not keto, but a Mediterranean diet has been associated with lower cholesterol and with brain health on several large studies.)

With no family history of Alzheimer's, you should view your life as full of healthy choices and options! Walking 30 minutes a day is great! How about adding intermittent high intensity to that walk, with a run for a few minutes, then walking, then a short jog, then walking, etc? Exercise is great for both our brains and hearts and has great benefits for anxiety and mood.

Your 85 year old grandfather sounds like a "Keep Calm and Carry On" chap; if you're nearby, spend some time asking him to tell you about his life, his grandparents and parents. We can learn our ancestry from people whose memories stretch back several generations before us even without Ancestry tests. Don't worry too much about your parents; they have those same healthy family genes and may surprise you by changing their habits as they see the benefits of what you do. We can only guide our own journey and have to let others make their own choices.
4/4 and still an optimist!


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