Compound Heterozygous C677T & A1298C

[MrME/CFS++]

Finaly I found a reasearch that suggests that compound is more common than not compound for having 677 and 1298 SNPs.

"Most studies have reported no or few cases with 677T and 1298C alleles in the cis configuration. 43,48,51,52 It is likely that these mutations arose independently on different alleles and recombination has not occurred frequently enough, within the requisite small interval, to place the two mutations on the same chromosome. Furthermore, a recombinant enzyme containing both the 677T and 1298C substitutions has the same activity as the recombinant enzyme containing only the 677T allele,27 suggesting that 677T/1298C homozygotes do not have decreased survival (compared to 677TT homozygotes)."

http://www.ncbi.nlm.nih.gov/books/NBK6561/

and..

"These homozygotes do not appear to have higher serum homocysteine levels than controls. However, individuals who are compound heterozygotes for the 1298C and 677T alleles tend to have a biochemical profile closer to that seen among 677C→T homozygotes, with increased serum homocysteine levels"

Which tells that compound variant is very close to homozygous 677 when we talk about homocysteine blood levels as an marker. Nothing said of the frequency of beeing compound 677 and 1298 though which is some kind of strange they not have testet/concluded, when they at the same time compare beeing compound 677 and 1298 with homozygous 677. It might be hidden in some tables though or elsewhere in the report, but cant find it. I think many people wants to know. Including me.

 

[Valentijn]

Finaly I found a reasearch that suggests that compound is more common than not compound for having 677 and 1298 SNPs.

Only one of the sources cited in that paper seems relevant: http://www.nature.com/jhg/journal/v48/n1/full/jhg20031a.html (full text at "Download PDF" on the right side).

It's a bit dubious, since they decided to throw out data from the UK and Canada, since it contradicted their conclusion. They chose to attribute the increased prevalence of the non-compound heterozygous mutations to a presumed "founder effect". They probably would not have excluded those studies if they didn't render the overall effects to be insignificant.

At the very least, this suggests that compound heterozygous mutations are not the more common in people from the UK, or of British ethnic origins. And it makes the broader assertion more dubious as well, since they had to filter out data to get something significant.

 

[MrME/CFS++]

It is likely that these mutations arose independently on different alleles and recombination has not occurred frequently enough, within the requisite small interval, to place the two mutations on the same chromosome

It might be this documentation...

http://www.nature.com/ejhg/journal/v10/n10/full/5200863a.html

If you read last part of bold text you see why recombined variants are rarer than combined ones. Its nothing that has to be documented, it is math. Thats why they write it like that. Its how mutations normaly develope in time, and in what order.

But since ANYTHING can happen with genes, they use words/phrases like "likely" or "the odds for". But normaly combinations is more common than recombinations. IF we asume that both polymorphisms started from two different persons in history. Which is also most logical.

 

[wolfmagic]

Compound Heterozygous = 70% under-functional
Nov '14, Ben Lynch wrote how he is Compound Heterozygous and it equates 70% loss of function (i wanted to post it last week when i the reference was handy, but this whack system requires days to approve a new poster and never notifies them when approved, so its no longer handy). I found it at the bottom closer of his writing on this page:

Preventing Methylfolate Side Effects - MTHFR.Net
http://mthfr.net/preventing-methylfolate-side-effects/2014/11/26/

... That is how I do it.

Remember, I am compound heterozygous MTHFR myself which means my MTHFR enzyme is reduced by about 70% in function.

Do I take methylfolate every day?
No. I take it when I feel mentally slow or use my brain heavily such as during conferences or writing long articles such as this (but I won’t take it now because it is midnight and time to go sleep. I don’t want my adrenals to get taxed…)

 

[jason30]

So when you are Heterozygous in C677T & A1298C then the focus is on methylfolate ?

"C677T
One function of MTHFR (Methylenetetrahydrofolate reductase) is to help convert homocysteine to methionine. A
MTHFR C677T mutation means that the MTHFR enzyme may have trouble performing its task leading to high levels
of homocysteine."

I wonder if methylfolate helps with converting homocysteine to methionine?