The power and pitfalls of omics part 2: epigenomics, transcriptomics and ME/CFS
Simon McGrath concludes his blog about the remarkable Prof George Davey Smith's smart ideas for understanding diseases, which may soon be applied to ME/CFS.
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23andMe results - help interpreting please!

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by nimo, Nov 4, 2014.

  1. nimo

    nimo

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    UK
    Hi all. I'm new here. I'm looking into methylation now that Lyme+coinfect treatment hasn't given me the improvements I'd hoped. I had my SNPs tested with 23&Me on a friend's advice, and can see that there are possible issues that give me hope of further improvement with treatment.

    I'd love some help with interpreting my SNPs from those further down this path than me. Brainfog is my number one problem, so it's taken me a while to compile this. I hope it includes everything and makes sense! Thanks in advance.

    A little background:

    1992 diagnosis: CFS/ME
    2008 diagnosis: mitochondrial dysfunction / krebs cycle dysfunction; vascular endothelial dysfunction; fructose intolerance; leaky gut
    2009 diagnosis: borrelia + babesia + bartonella + ehrlichia (i.e. Lyme & co-infections)

    Have improved some since treating above, but still pretty much housebound.

    Primary symptoms: brainfog (no 1!); depersonalisation; anxiety, or it's flipside - lethargy and apathy; mood swings; sleep problems - unrefreshing, wakeful ; poor short-term memory; poor short-term memory (sorry - couldn't resist! ;-) ); poor energy levels; reflux; high intraocular pressure & visual snow; sore feet & calves, & occasionally hands; hair loss on back of calves; plaque psoriasis & soft, creping skin, occasional smell of ammonia in sweat and sulphur in urine, also rarely ‘maple syrup’ smell in sweat (NB have not ingested MS – am on sugar free diet)

    A lot of my symptoms come together - anxiety, wakefulness, sore feet & calves, sulphurous urine smell often ramp up together, and seem cyclical. I had assumed die-off of lyme or coinfection, but they don't seem to fit a rigid cycle, so wonder if there might be another explanation.

    Common bloodwork results: usually low uric acid, occasionally low phosphate
    ______________________________________________________________________

    So here are my Yasko SNPs, the 23&Me data is from the V4 chip. I have run the data through the following reports: Genetic Genie, Sterling's and Promethease. There are so many, I wasn't sure which to put. In the end I've picked out SNPs from Yasko's list regardless of result, and then added from Sterling's Methylation list where anything other than -/-. Where the Sterling's 'extra' is for the same gene as in Yasko's list - I've added in brackets in Yasko's list, otherwise the Sterling's 'extras' are in a separate list below.

    COMT V158M -/-
    COMT H62H -/-
    COMT 61 (P199P) -/-
    (Sterling's = COMT @rs6269 +/+)

    VDR Taq Tt
    VDR Fok Ff (Question over risk allele? "Risk Allele: T, 23andMe: A" Source: http://www.snpedia.com/index.php/Yasko_Methylation#VDR_Gene) (I'm AG)
    (Sterling's = VDR Bsm +/-)

    MAO A R297R +/+

    ACAT 1-02 -/-

    MTHFR C677T +/-
    MTHFR 3 (P39P) -/-
    MTHFR A1298C -/-
    (Sterling's = MTHFR @rs3737964 & @rs4846048 both +/-)

    MTR A2756G +/-

    MTRR A66G +/-
    MTRR K350A -/-
    MTRR 11 (A664A) -/-
    (Sterling's = MTRR @rs3776467 +/-)

    BHMT 2 -/-
    BHMT 8 +/-
    (Sterling's = BHMT R239Q +/-)

    AHCY 1 -/-
    AHCY 19 -/-

    CBS C699T +/+
    CBS A360A -/-
    (Sterling's = CBS A13637G & C19150T both +/+)

    I realise that I miss out on some of Yasko's list due to 23&Me V4 chip – BHMT 1, BHMT 4, SHMT C1420T, SUOX S370S, NOS D298E etc.

    The following are not in Yasko's list, but are in Sterling's Methylation list (where not -/-). I don't know which are relevant variants:

    ACE Del16 +/+
    ADD1 G460W +/-
    DAO @rs3741775 +/-
    FOLR2 +/-
    GAD1 @ rs769407 +/-
    GAD1 @ rs3791851 +/-
    GAD1 @ rs12185692 +/-
    GAD1 @ rs3791878 +/-
    GAD1 @ rs10432420 +/-
    GAD1 @ rs3828275 +/-
    GAD1 @ rs701492 +/-
    MTHFD1 G1958A +/-
    MTHFD1L @rs17349743 +/-
    MTHFD1L @rs803422 +/-
    MTHFS +/+
    NOS2 @rs2274894 +/-
    NOS2 @rs2248814 +/-
    NOS3 @rs3918188+/+
    PEMT @rs4646406 +/+
    SHMT2 @ rs34095989 +/+
    TCN1 +/-

    The following are my detox SNPs from Sterling’s (where not -/-) in case any are relevant to the methylation SNP interpretation.

    CYP1B1 L432V +/-
    CYP1B1 N453S +/-
    CYP1B1 R48G +/-
    CYP2C19*17 +/+
    CYP2D6 S486T +/-
    CYP2D6 T2850C +/-
    GSTP I105V +/-
    NAT2 A803G (K268R) +/-
    NAT2 G590A (R197Q) +/-
    NAT2 T341C (I114T) +/-
    SOD2 +/-
    SOD2 A16V +/-
    PON1 Q192R +/-

    Q1 - any comments on my SNPs and any explanations for my symptoms based on them would be most welcome!

    Here is my (beginner's) simplistic interpretation based on looking at Yasko's Methylation Pathway diagram (and assuming the genes are expressed) : MTHFR, MTR, MTRR could be impacting normal function of the full cycle, BHMT could be impacting normal function of the shortcut, CBS could be 'draining the bath' (see also Q3 below). GST/SOD/GAD could be causing poor detox and/or excitotoxicity (I'm not sure if my SNPs are the relevant ones)? GAD?/MAO A/ACE could be causing neurotransmitter issues (again, not sure of relevancy of GAD1 SNP variants reported. Please see Q2)? Please confirm I'm on the right track / add to / pick apart!

    ______________________________________________________________________

    Yasko’s Methylation Pathway diagram - there are some others on this that are not on her list. Some may be on Sterling's, but not obvious which variant. I realise I don't need to know all the SNPs on the diagram as you don't need to rectify some, but I think some of them will be useful to know (GAD, GST, SOD in particular from what I've read so far), and I'd be interested to know anyway. I'd like to put a tick next to the problematic genes on Yasko’s Methylation Pathway diagram to aid understanding, and I’m not sure which variants I should be looking for within the following:

    OTC
    NOS (NOS2/3? Either, both?)
    GST (GSTM/P as found under detox? Either, both?)
    SOD (SOD2/3 as found under detox? Either, both?)
    DHPR
    MAT
    G6PDH
    GAD (GAD1? 7 out of 11 GAD1 variants on Sterling's are +/-, the others are -/-)
    SUOX
    ACAT
    SHMT
    AHCY

    Q2 - does anyone know the relevant variants for these & their rsID #s if on 23&Me V4 chip? Which of these, and those above Q1 that Yasko doesn't list, are relevant? I guess I'd like to produce a useful forum sig with my relevant SNPs.
    ______________________________________________________________________

    I have found the following in Promethease that is not on Yasko’s MP diagram and is under Tongue Tie/Cleft Palate in Sterling’s:

    CTH S4031l (rs1021737) +/+

    It codes for cystathionine gamma-lyase (confusingly, the enzyme is also referred to as CGL and CSE) which breaks down cystathionine into cysteine and alpha-ketobutyrate, and possibly ammonia, and also breaks down cysteine into ammonia and hydrogen sulphide.

    http://en.wikipedia.org/wiki/Cystathionine_gamma-lyase

    Q3a - I realise I'm new at all this, but does anyone else think this should be under Methylation in Sterling’s? And appear in Yasko’s diagram (I'm sure not every SNP involved in methylation will be, but this seems important)? Cystathionine seems highly relevant to the pathway.

    Q3b - if CBS SNPs are an upregulation, and this CTH SNP is a downregulation - isn't that going to produce a bottleneck between the two? Implications?


    Q3c - can anyone confirm ammonia comes from cystathionine and not just cysteine?

    Q3d - how does CTH affect the regular advice for CBS SNP management? Freddd suggests avoiding glutathione and it's precursors. I would think CTH would affect this advice?

    ______________________________________________________________________

    Q4 - Are there any more relevant SNPs I should be looking for (outside of those discussed)?
    ______________________________________________________________________

    Q5 - anything else?

    Thanks again.

    Nick
     
    Last edited: Nov 4, 2014
  2. student

    student Senior Member

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    (Ah, sorry I haven’t a cloo about your Lyme! Just overread that) Though:

    D 3 can easily be supplemented. (A) ACE/ comt –Mao. (B) Mt r RR- group



    Go through these in Groups – after low & slow start. Yes, you do learn a lot here. Right from start.. (VDR’s - for D3, help regulate your Keton and blood sugar = some keys to the Energy system)…

    (1) ACE, Comt – than go to- Mao. Your Mao +/+ will get strong influences by more ACE/ Comt’s SNp‘s …

    (2) Take Mthf Mtr mtRR – as a group. Mthf 67 plus

    Mao – needs B2, - slow Neurotransmitter breakdown (= overstimulations) / go low and slow.

    Mao plus ACE – Anxiety and Frustrations.

    Mao plus Comt – Dopamin fluctuation. = swinging moods.



    // now start this 2.nd groop: start with MTHf

    The MTHf .29 SNp gives - depression, bowls, fatigue. ME, dementia, pain…

    The .67 SNp- Series … (with high homocyctein spilling, an overflow of this most costly fuel / =strong Metylation Blockage ). The centerpiece: Clotting, vein thrombosis, stroke, heart disease, (vascular placental problems, in pregnancy, preeclampsia) neural tube defects, lip cleft.

    In combination: 67. 29 both MTHf -/+; stronger one +/+ (1x), worsening with both +/+ +/+ (2x)

    Ad others…

    @nimo what ever I write – I do hesitate much, because I do see so many factors for

    Heavy leaky gut coming up ! Please look for the more general guidlines. Do not start much – whatever you think – and continue to go verry low in your methylation. Perhabs postpone much of this for the better and later times.

    FIR sauna can be your good option. (Buy the Carbon heater panel and I put that into my used 4 men tend. Second electro- heater with only 32 Celcius aimed. Not eaven swet much). My own costs were about 100 $.

    Nutrition will be your other key. Try to find your way and fiddel through to your verry slow uppbuilding process. Do not give up – but please do everything with the guts first. ACat Shmt and CBS SNps are mentioned – as first priority in this. Mrs. Caledonia @ Forum offers a beginners link. with 4 R gut treatment. As PDF download.

    Brain fog: Try to read about Ornithin (Arginin) for exampel at night, much liver support in nutrition is needed. And many minor stepps that can keep your Amonia down. Do you use urin sulfat sticks measurements (to avoid sulfite)? Free tiol avoiding – diets are mentioned.

    High doses of B 1 (3x 300), or I did use Depyroll basis kapsule (but on methylation – you go much lower / 1/ 5 th of the dosage). Lately I tryed curcuma (plus pepper, in oil). I would take a very small dose sublingual. Place under the tongue every 20 minutes. (See what helps – and go and tell others.)


    student :hug:hugs

    ps. How are you. Is anything stable yet?

    It could be an option- just supplement B12 (hydroxi 3000mg per week) Injektion, Magnesium 2x 400mg daily for 3 weeks. Plus D3 at least 2000iE for 3- 4 weeks. There must be ways to - supplement well. Just while you do Guts. guts. guts - and not jet start the methylation it self. No? - please grow in understanding. - and never give up!! That way you would avoid the Folat suplement. So it will not be high methylation that could start.
     
  3. student

    student Senior Member

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    See also the verry far… botom one on this list: Shmt „14“ SNPs will help building the new DNA for Mitosis, leaky gut can be prevented, your Endothelium will start closing, this is important in the gut surface. (Potassium can be needed and Glutathion is used up for the interior of new cells). This shift is away from the processing of homocysteine to methionine.

    I have a dream: Cbs, Acat and shmt – were said to be the core SNp groop of your first priority intrests. If this ever becomes possible, to creat calm bowl @methylation start, than the hole therapie process could be the much better bal game. please - do care for this background.

    (Yes we learn here, MthFR has become very influential with quantity of its disease and symptoms.)
    Though the core theory is to lift this cbs Block in the methylation pathway. Sidepassing this block has become important for those that have the CBS SNps. An overspill of good methylation Material (as the homocystein) was in the past not well prevented. So keep low and slow. Change of Food and slow care for infektion is crucial. Do this ground work before you start with quick changes, that your methylation process will need.

    The methylation theapie will later not be very stable. A need for urgent thearpie advice will often come up. On the other hand not many doctors have already done this in the past. So you will verry soon have to find your own doctor that supports all this process. He should do the basique blood tests. (And to all of you how read here:- You have to get this 23&me results with your genetic SNps early in this therapie. Yes, it is costly.)

    Take your time now to go into the food advice. Do the changes soon. It will often be the small quality questions. Raw &vegies, Yes. Though in ceartain extreem situations, there will be much more to it: see http://www.drmyhill.co.uk/wiki/Category:Bowel_Problems

    Dr. S. Myhill (UK) gives a kind of house doctors („hausarzt“) advices, that we do sometimes need. I was given her book. It contains much practical advice for my cfs fatigue. The german cfs fatigo convetion published that. She goes into therapie advice (translated fatigo.de journal NO: 23). She would still give meat and protein http://www.drmyhill.co.uk/wiki/Stone_Age_Diet_-_this_is_a_diet_which_we_all_should_follow . Just click through the topics http://www.drmyhill.co.uk/wiki/Category:Nutrition,_Vitamins,_Minerals_and_Diets . Later – when stuck, you get advice to lower the sulfite. M. Pall is a source for that. Your mesurment can be urin sulfat (sticks). It can be difficult to sort out this „Thiol free“ diets. There is a big chunk to learn – here.

    Good luck, big hugs :hug: yours student
     

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