James Coyne “lays waste” to PACE trial in Edinburgh
Sasha summarises Professor James Coyne's recent no-holds-barred talk on the PACE trial and points you to the slides, video, audio and transcript.
Discuss the article on the Forums.

SNPs for Dihydrofolate Reductase (DHFR)

Discussion in 'Genetic Testing and SNPs' started by nandixon, Sep 25, 2012.

  1. Bluebell

    Bluebell Senior Member

    Messages:
    392
    Likes:
    214
    Valentijn, I believe that you misunderstood what NanDixon said about Richvank's results.

    You have indicated in your table here that Rich's result for rs1650697 was AA. However, that is what NanDixon said HER result was. She stated that rs1650697 was the only one where she differed from Rich's.

    She also stated that Rich's results were all homozygous and all "-/-", so that probably means that Rich's result on rs1650697 was GG, the only other possibility if NanDixon's "+/+" AA homozygous result was different from his.

    In her original post, she wrote: "....his results appear to be completely normal (homozygous -/- throughout). Mine are identical to his with only one exception: the SNP rs1650697 (aka C35T or G-437A) that overlaps with a coding region for the gene MSH3 is homozygous (+/+) for the variant alleles (AA)....
    Below are my results for people to compare to theirs.... rs1650697 AA (+/+)."

    I have not tried to search for the thread where Rich reported his original 23andme results, but that would be the best way to make sure, of course. :)
     
    Valentijn likes this.
  2. Bluebell

    Bluebell Senior Member

    Messages:
    392
    Likes:
    214
    Sea, I also have a CT at rs10072026, just like you --
    and otherwise, like you, I match Rich's results
    (if NanDixon was saying that Rich's rs1650697 was GG -- see the preceding post I made about that rs number -- which is also my result on that one, GG).

    As far as I can tell on DBsnp, the CT at rs10072026 was in about 20% of a European sample, but was not very common in other samples of ethnic groups that are listed there.
     
    Sea likes this.
  3. Bluebell

    Bluebell Senior Member

    Messages:
    392
    Likes:
    214
    For the past couple of months, I've been struggling to drink 1 or 2 cups of green tea a day (I find the taste unpleasant, even when I mask it in a brew of other types of tea) and I don't think I feel better on any health dimension from drinking it (although I can't know what it might be doing internally-fighting potential cancer etc.), and when I applied it to my face as a toner once daily over 2 days, it stung and dried out my skin, so I'm not sure that green tea is for me. I would like to stop drinking it... I've read such overwhelmingly-positive reports of its health-giving properties that I was interested to learn here that it inhibits the production of BH4 (via DHFR). Yesterday I read that it reduces the absorption of thiamin (B1) and folate (B9), plus of course iron.
     
    Gondwanaland likes this.
  4. nandixon

    nandixon Senior Member

    Messages:
    604
    Likes:
    1,096
    That's right. The post where Rich gave his SNPs for DHFR is located here:
    http://forums.phoenixrising.me/inde...ies-please-post-here.14115/page-2#post-233836
     
    Valentijn likes this.
  5. roxie60

    roxie60 Senior Member

    Messages:
    1,786
    Likes:
    593
    Central Illinois, USA
    Mine are the same as Nan's except for the last one I am AG which means I am exactly the same as Drex. I look forward to the GCH1 thread.....if it already exists can someone add the link plz
     
  6. ukxmrv

    ukxmrv Senior Member

    Messages:
    4,056
    Likes:
    3,363
    London
    Here's mine but I am late to this thread and don't have a clue what it all means

    rs7387 TT
    rs1643659 TT
    rs1677693 GG
    rs1643649 TT
    rs11951910 TT
    rs865646 GG
    rs13161245 --
    rs10072026 TT
    rs11490741 CC
    rs863215 CC
    rs1478834 CC
    rs1650697 AG
     
  7. LynnD

    LynnD

    Messages:
    26
    Likes:
    0
    Mine are the same as Val's.
    Anyone try food or supplements to see if beneficial for this snp's?
     
  8. trollo

    trollo Senior Member

    Messages:
    130
    Likes:
    18
    Italy
    These are mine:

    rs7387 A or T AT (+/-)
    rs1643659 C or T CT (+/-)
    rs1677693 G or T GT (+/-)
    rs1643649 C or T CT (+/-)
    rs11951910 C or T TT (-/-)
    rs865646 G or T TT (+/+)
    rs13161245 A or G no call
    rs10072026 C or T TT (-/-)
    rs11490741 C or T CC (-/-)
    rs863215 C or T CT (+/-)
    rs1478834 A or C AC (+/-)
    rs1650697 A or G GG (-/-) p.s i corrected this as Valentjin made me do a mistake...

    Please can somebody explain to me what that means?? Does this mean i could have low BH4 recicling via DHFR??
     
    Last edited: Apr 18, 2014
  9. trollo

    trollo Senior Member

    Messages:
    130
    Likes:
    18
    Italy
    But i yet haven't understood if there are any known deleterious DHFR snps already linked with issues by studies.
     
    Last edited: Apr 19, 2014
  10. aquariusgirl

    aquariusgirl Senior Member

    Messages:
    1,218
    Likes:
    275
    Hmm, why would my mom only have 5 snps on that gene?
     
  11. Valentijn

    Valentijn Activity Level: 3

    Messages:
    11,846
    Likes:
    30,039
    Newer chip?
     
  12. Gondwanaland

    Gondwanaland Senior Member

    Messages:
    3,685
    Likes:
    2,589
    Interesting. My husband is +/- to many of these SNPs. He benefits from Royal Jelly instantaneously. I have always been puzzled by the fact that RJ does nothing for me since many of my SNPs point to BH4 deficiency.

    nandixon's ; myself ; my husband
    DHFR SNPs:
    rs7387 A or T TT (-/-) not available
    rs1643659 C or T TT (-/-) TT ; CT
    rs1677693 G or T GG (-/-) GG ; GT
    rs1643649 C or T TT (-/-) TT ; CT
    rs11951910 C or T TT (-/-) n.a.
    rs865646 G or T GG (-/-) GG ; GT
    rs13161245 A or G AA (-/-) n.a.
    rs10072026 C or T TT (-/-) n.a.
    rs11490741 C or T CC (-/-) n.a.
    rs863215 C or T CC (-/-) n.a.
    rs1478834 A or C CC (-/-) n.a.
    DHFR, MSH3 rs1650697 A or G AA (+/+; 4% frequency) AG ; GG
     
  13. Envista

    Envista

    Messages:
    2
    Likes:
    1
    Hi Nandixon, whilst this was posted a few years ago I see you're still an active member. You seem to really know your biochemistry. I have a question for you....

    There are two ways to convert dihydrobiopterin (BH2) to tetrahydrobiopterin (BH4). I'm mostly interested in with the DHFR involvement and recently attended a seminar on "Methylation". They suggested that BH4 is 'methylated', thus a carbon group (CH3) is added to BH2 to make BH4. To quote specifically from the manual provided: "by donating a methyl group from folate to create tetrahydrobiopterin (BH4), used for the synthesis of certain monoamines". However upon hours of internet research I haven't found that to be true, I've only found that Folate (in the form of THF) donates a Hydrogen to BH2.

    I'd be interested in your opinion. Thanks.
     
    nandixon likes this.
  14. alicec

    alicec Senior Member

    Messages:
    922
    Likes:
    1,427
    Australia
    That's not correct. The enzyme DHFR is a reductase not a methyl transferase; electrons (in the form of hydrogen) are transferred, not single carbon units.

    The names of the substrates and products give the answer. Dihydrofolate is converted to tetrahydrofolate, dihydrobiopterin is converted to tetrahydrobiopterin. The reduced substrates, ie the products of the reduction reaction, have two additional hydrogens.
     
    Last edited: Nov 1, 2016
    Valentijn and nandixon like this.
  15. Envista

    Envista

    Messages:
    2
    Likes:
    1
    Actually if you go to http://www.altmedrev.com/publications/13/3/216.pdf Figure 4 you'll see that 5MTHF (activated form of Folic acid) converts to Methylene THF to form BH4, the difference in structure is one less hydrogen on Methylene THF. So whilst a 'Methyl group' wasn't transferred, 5MTHF seems to have donated a hydrogen and is certainly involved. The second figure on Figure 4 shows THF converting to DHF in the production of BH4 - what's occurred here?

    Interestingly the article also states 5MTHF is similar in molecular structure to BH4 and can substitute for it in low BH4 conditions, "The chemical structures of BH4 and 5-MTHF are similar enough that eNOS will accept 5-MTHF as a substitute cofactor (Figure 5).39 A similar mechanism might be at play in the antidepressant effect of folate. This author hypothesises that 5-MTHF might substitute for BH4 in the hydroxylase enzymes involved in monoamine neurotransmitter synthesis".

    So judging from a manual I was given during a Methylation seminar, we can definitely agree the following is incorrect, "5MTHF donates it's methyl group for the creation of BH4"
     
    Last edited: Nov 2, 2016
  16. nandixon

    nandixon Senior Member

    Messages:
    604
    Likes:
    1,096
    The upper part of Figure 4 is showing the transformation of "qBH" into BH4 by having the MTHFR enzyme run in reverse. qBH2 is quinoid-dihydrobiopterin, which is a very similar but different molecule than dihydrobiopterin (i.e., BH2). (Note that the structure of methylene-THF actually has 2 less hydrogens than 5-MTHF. The loss of the other hydrogen just isn't being shown in the cartoon figure.)

    For more about MTHFR running in reverse, see this old post of mine:
    http://forums.phoenixrising.me/inde...sive-cbs-ammonia-fix.31835/page-2#post-500142

    In the lower part of Figure 4, this is just showing the recycling of BH2 to BH4 by DHFR. (The diagram is also indicating that qBH2 can spontaneously rearrange to form BH2, which is correct.)
     
  17. alicec

    alicec Senior Member

    Messages:
    922
    Likes:
    1,427
    Australia
    @nandixon just answered, so I'll simply add the following.

    As far as I am aware, that single in vitro study by Kaufmann is what everyone relies on to claim that MTHFR runs backwards. That was in an artificial laboratory creation. There is no evidence that it does this in the body and if you look at any text book or general article on the folate cycle you will see that the MTHFR reaction is one of the forward only reactions in the cycle (some other parts can go in two directions depending on cellular circumstances).

    I've uploaded a diagram to illustrate this.

    Here is an older post of mine which discusses a number of inaccuracies in the article you linked.
     

    Attached Files:

    Valentijn and nandixon like this.

See more popular forum discussions.

Share This Page