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Interesting MTHFR Variations

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15,786
That last sentence was just antagonistic, demeaning, and unfriendly.
Unlike your own post? Frankly my response was rather mild, all things considered:
Maybe, it seems, you might think you are the teacher? You seem to be referring to people here as your audience.

It just shows that if you do not even have a basic understanding of the vocabulary and maybe you should be a bit more humble regarding your knowledge about the subject in general.

Do you assume you have more knowledge than anyone else who comes here? If so, what are your credentials? Until then you are not my teacher, just another random person on the internet who might or might not know what they are talking about.
 

Flo

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Unlike your own post? Frankly my response was rather mild, all things considered:

I like when people admit to doing something wrong and use another persons actions to justify it.

Valentijin, I cannot interact with you anymore. I do not have the energy for the uncooperative.
 
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@Valentijn

Have studied my MTHFR gene again and find that I have 4 homozygous SNP's of your "very rare" list. One of them are pathogenic (MTHFR rs45590836 M581I - 23andme = C:C). Else I have totally 7 homozygous SNP's in MTHFR. Here is rest of my very rare homozygous list, I asume the rarity will state as real mutations for those?

MTHFR rs45590836 M581I
MTHFR rs3927589 E423D
MTHFR rs45550133 R134C
MTHFR rs2066472 R68Q

In addition I have the unpleasant compound C677T and A1298C combination which Dr Lync lately claims has been upgraded with a new status of gene expression from 50% loss to now 70% loss of function. I have asked him for a link to where he read that, and awaiting the answere from him. If its true its very significant and should be more of a priority to researcher as it often includes a ton more symptoms than the C677T does. This is my thinking of all that I read though. Here is what he states. Just search "70%" within article:

http://mthfr.net/is-mthfr-related-to-x-condition-x-disease-x-symptom-x-syndrome/2015/06/10/

I have some questions for you:

1. Why does they not conclude the C677T polymorphism as pathogenic with all the research that show this variant with elevated homocystein (homo)? Do you have a clue for what the requirements for geting the "pathogenic" status are? I wonder because how could the M581I mutation get this status with almost no research behind it. I dont see the logic here...

2. Could you confirm to me that my M581I is homozygous with my aleles C:C? And if C:C IS the pathogenic variant? One report I have (claims it is.

3. Can you confirm that the C677T SNP today should be called C665T, and the A1298C SNP today should be called A1286C? If true, what happend, and should we all use the new gene names, here and other places on internet?
 
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Messages
15,786
Have studied my MTHFR gene again and find that I have 4 homozygous SNP's of your "very rare" list. One of them are pathogenic (MTHFR rs45590836 M581I - 23andme = C:C).
In my list on the previous page you'll see that the problematic version is "TT". Simply being homozygous is not the same thing. The CC version which you have is the extremely common and normal version.

In addition I have the unpleasant compound C677T and A1298C combination which Dr Lync lately claims has been upgraded with a new status of gene expression from 50% loss to now 70% loss of function.
You cannot guess that it is compound heterozygous. In some ethnic populations that might be more likely, but it sounds like it's more likely not to be compound heterozygous in people of British descent. At any rate, it's a conclusion that can't really be reached without more data than 23andMe provides ... though if you have 23andMe data from your parents, it might be clearer.

1. Why does they not conclude the C677T polymorphism as pathogenic with all the research that show this variant with elevated homocystein (homo)?
Because MTHFR mutations aren't a big deal even when reducing gene function to 30% of normal. When it gets down to 10% or less, that's going to be a bigger problem. But people who are +/+ for MTHFR C677T or compound heterozygous for C677T and A1298C only face a mildly elevated risk of certain diseases - meaning the mutations do not cause diseases themselves.

And the most studied risk is in folate-related birth defects in the offspring of mothers with those mutations. In addition to the risk being relatively small, a few studies have shown that supplementing with a multivitamin or eating a decent amount of vegetables completed removed the elevated risk level. So the bad effects of MTHFR C677T and A1298C are effectively neutralized with a healthy diet, and there's really only a problem if people with those mutations are eating a pretty poor diet.
 
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You cannot guess that it is compound heterozygous
Well, just got back my result from official health care center that confirmed it for me. I asked my geneticist there and he also said that compound are more common than recombined variants. To develope recombined variants to be more common than the original compound variant is also almost impossible. The high number of compound variants is evidence of that the recombined version never started from one person. Which also would be a hell of an coincidence if it survived evolution, cause the chance for it to "disapear" (die out) is huge. Only when the population have been VERY common with both variant you will start to develope some cases of recombinations that spreads out in the popullation.

I feel you are pretty naive if you think MTHFR gene polymorphisms only comes down to homocysteine levels and cardiovascular issues. Homocysteine may not be the culprit at all with MTHFR. Just an marker for some lucky people if they found out early in life. And for those it doesnt show up for (hard enough), it does not say anything about the status inside every cell in theire body, where MTHFR genes are suppose to work at 100%. I like to see MTHFR as every cells engine. Everybody understands that an engine working at 30% will have issues all over its components. And if you charge that engine with something, everybody knows that the chance for it to halt is far more the case than if it provided 100%. This is what happens in a body with cells working at 30%. If you develope issues because of poor efficiency in every cell the 30% working MTHFR gene (and the holde cell) will struggle real hard. Without methylation we all know that death is near. No cell can work without it.

Noone should simplify the meaning and importance of the MTHFR gene. You may not like (have a feeling) SNPedia, but this link shows you how severe (from a readers side) only the 677 SNP has been researched to create problems. And you can read the 2300 PubMed research wich is mentioned inside to find more problems. Its not hard to see that researcher really are interested in these MTHFR SNP's and the significant amount of issues connected to them. And every day I find new research that is poping up. Something tells me the odds for them to get the "patogenic" status will come some day. Today the status for the MTHFR T677T is ** With Uncertain significance allele ** - http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=1801133

http://www.snpedia.com/index.php/Rs1801133

I did not double check my 3HCenko report that reported me beeing ++ for MTHFR M581I. Focused on the red ++ instead of the CC. Sorry for that. Will take it with the report makers.

Have quit all grains and diary products. Vegetables and healthy food has by itself (because of severe symptoms) been daily diet for decades. Does not touch alcohole or rafined sugar. Nope, my symptoms did not vanish.

What about my 3. question? Is it normal to "rename" SNP names? And why do they do that, if its a fact. Has something been discovered in between? I find lots of research and stuf when searching the new names of 677 and 1298...
 
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15,786
I feel you are pretty naive if you think MTHFR gene polymorphisms only comes down to homocysteine levels and cardiovascular issues.
Well then, I guess you've got it all figured out and don't want to ask me any questions after all. Get as excited as you want over having a very common variant, it's really not of any concern to me.