New member any others iron disorders H63D and APOE3/4

[jason1635]

Hello--

Like some of you wish I had not done the 23 and me test. I was dx years ago with H63D hemochromatosis and treatment (blood donations) helped a lot with symptoms. What does this do to risk likelihood?

Recently did 23 and me mostly for ancestory--didn't know they checked for AD and other neuro diseases and got results back saying I had one variant at APOE 4.

Does anyone have any info on interplay between these two variants--guessing it has negative implications but didn't find much.

I am 43 in fairly decent health with high LDL only and no real family history of AD under 85. Where do you go from here. Really depressed tonight but want to start tomorrow on a positive track

[NF52]

Hello--
Like some of you wish I had not done the 23 and me test. I was dx years ago with H63D hemochromatosis and treatment (blood donations) helped a lot with symptoms...
Recently did 23 and me...I had one variant at APOE 4.

Does anyone have any info on interplay between these two variants--guessing it has negative implications but didn't find much.

I am 43 in fairly decent health with high LDL only and no real family history of AD under 85. Where do you go from here. Really depressed tonight but want to start tomorrow on a positive track

Hi Jason,

I admire your determination to start tomorrow on a positive note--so will see if I can help you get there, with the caveat that this comes from fairly quick search of recent articles on H53D (and other HFE genes) and risk of Alzheimer's disease (AD) , vascular dementia (VD) and other neurodegenerative diseases.

Here are some key points and the reference for an article that may be helpful (if a little dense with science--a recurring "problem" with scientific articles, it seems!)
This is from March 2018: The bottom line here seems to be that in an Italian study of patients with a mean age of 78, and either AD, VD, or Mild Cognitive Impairment, no additional risk was seen with H63D for Apoe4, even though other studies have found some increased risk.

The HFE H63D polymorphism did not show any significant risk fluctuation in our study, though it has been reported a higher rate of the 63D-allele in neurodegenerative disease [85], also in combination with different APOE isoforms [86–88], suggesting H63D a genetic risk factor for neurodegenerative diseases [89]. Conversely, the same metanalysis of Lin et al. supported a slight protective role of H63D [37], underlying the still conflicting results.

[Emphasis added.] Gene-gene interactions among coding genes of iron-homeostasis proteins and APOE-alleles in cognitive impairment diseases

There are articles that suggest an additional risk factor for some people, but H63D is common, at about 25% of people with European ancestry, and does not seem to always cause HE. That suggests that it may be multiple genetic or environmental factors required to get what seems to be H63D as the sole culprit in working with ApoE 4.

I found no article that stratified people with H63D based on whether it had been treated with chelation or blood donation. Since this gene was only identified in 1996 (or so) and these studies were on people in their 60's and older, I suspect that many were only genotyped for both ApoE and H63D late in life. That's like grouping people with undiagnosed diabetes to identify the risk for those with tightly managed diabetes.

It appears that this is an area of growing research. That is good news for someone who is 43 and in good health! Might be useful to stay involved with HFE advocacy groups regarding research and even future clinical trials, especially as you approach 55-60.

With no family history under 85, it's likely that you are like the happy Italians, cited above, who have no additional risk from H63D. And as a male with ApoE 3/4, if you were 20 years older than you are, you'd still only have a 20-25% risk of either MCI or AD by the age of 85.

So have a happy tomorrow (or today), and know that your age, your good health and medical treatment so far, and your family history are all likely to keep you smiling to a happy very old age!

[Gillyp]

Jason, welcome to the ApoE4.info site. Congratulations on both your courage for testing and your determination to move forward, grounded in positivity. There's not much that I can add at this point to what NF52 has found and shared. You'll find so much information on this site that may be helpful to you and you can certainly find lots of positive support from all of us. If you haven't already seen our Primer it's a great place to start. You can also search under different topics that may be of interest to you. Keep posting and welcome once again.

[jason1635]

Thank you very much NF52 for the inspiration, positivity, and recommendations for action. That is exactly what I needed today to start my journey. I appreciate you taking the time to both care and share, I am forever in your debt. H63D has some sinister neuro connections of its own, so have been done this road before but managed it, the APOE4 gene is just another ingredient to throw in the soup about managing health for myself and family. THANK YOU!

[Dan Parkie 234]

Hi Jason,
Yes, I am H63D and APOE 3/4. I hope that once you get over the shock of learning your risks you will have a chance to understand that you have so much to be grateful for. It's great to be smart and lucky! You made a brilliant move by signing up for 23andMe to discover your genetic risks. You are incredibly lucky to have risk factors for two diseases that can be treated, but could be fatal if they go undetected and untreated. Stick with this crowd; this forum is your gateway to the future of medicine!
Dan Parkie 234

[jason1635]

Thanks Dan, do you do anything specific because of the combination of the two mutations or just treat both independently. The data provided above is great and somewhat positive--not a lot of positives out there about H63D, other than relatively light iron loading. You are right I am thankful to know and modify behavior and treatment in middle age. Thanks for your kindness and positivity!

[Dan Parkie 234]

I was called "middle aged" by Dr. Iwan Nantschev on YouTube. It's on the internet, so it must be true! www.youtube.com/watch?v=_Bluf4pk86s&feature (copy and paste). My cameo role starts at 11:13. Don't blink; I'm only on camera for 5 seconds.

[slacker]

Here's an explanation from Stanford at the Tech on H63D, neurodegenerative dz, and hereditary hemochromatosis.

There's also been chatter on ferritin and iron blood levels on our website. Here is one topic you may find helpful.

[SunnySky]

Hi, there.

DH is only heterozygous H63D; he has both variants of APOE4, though.
His younger brother died 2.5 yrs ago from liver complications due to years of undiagnosed hemochromatosis. By the time the Dr realized it was HH, too much damage already took place. I don't know his specific SNPs, but he must have included H63D... also, di not know his APOE4 mutations either.

Keep ferritin down to 50 or below. It's my understanding that the ferritin measured in a lab is ' is actually a measure of the damage caused by iron stores. The ferritin protein in serum is the empty shell of the ferritin protein that was in the organ storing iron. The iron it stored has been released due to damage to the organ or inability of the organ to maintain the ferritin carrying protein in it's healthy form, and is essentially now dangerous free radical iron.
Also serum ferritin is never used in the body - only ferritin within tissues is used by the body. And this is only used when there is insufficient serum iron needed to make haemoglobin and new blood cells. Serum ferritin is lowered as a result of tissue ferritin being used, because this results in less tissue damage and therefore fewer "empty shell" ferritin molecules in the serum.
Ferritin has NO RELEVANCE to anything, truth be known...
Ferroxidase is the MASTER Anti-Oxidant Enzyme to REGULATE Iron. '

Have you had a full iron panel, and not just ferritin lab test?

[Greenman222]

Interesting to note in the UK. The NHS will not
Test for the APOE4 mutation. As they believe there is not enough evidence of a link between other mutations. Such as the Homozygous HFE H63D and the APOE4 causing memory problems and earlier onset Alzheimer’s.