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Valentijn & Caledonia - Please Help, 23&ME Results

Discussion in 'Genetic Testing and SNPs' started by redviper, Nov 27, 2013.

  1. redviper

    redviper

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    Hey everyone,

    I've been lurking in this forum for the past couple of months, just trying to learn as much as possible from some of the guru's here regarding SNP's. I just got my 23&ME results earlier today and I've noticed that both Valentijn and Caledonia give excellent advice for beginners, so I was hoping that perhaps you could take a quick look over my results. Any preliminary feedback or suggestions that you could provide would be greatly appreciated :)

    Methylation Analysis Results

    Homozygous Mutations

    MAO-A R297: +/+
    VDR BSM: +/+

    Heterozygous Mutations

    CBS A360A: +/-
    MTHFR C677T: +/-
    COMT V158: +/-
    COMT H62H: +/-

    Detox Profile Analysis

    Heterozygous Mutations

    CYP1A2 164A>C: +/-
    CYP1B1 L432V: +/-
    CYP1B1 N453S: +/-
    CYP2C9*2 C430T: +/-
    CYP2D6 S486T: +/-
    CYP2D6 100C>T: +/-
    CYP2E1*1B 9896C>G: +/-
    GSTP1 I1O5V: +/-
    SOD2 A16V: +/-
    NAT2 I114T: +/-
    NAT2 R197Q: +/-
    NAT2 K268R: +/-
    Just in case anyone is wondering, I'm a 28 year old male that has been suffering from severe CFS/ME for two years.

    Thanks :)
  2. taniaaust1

    taniaaust1 Senior Member

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    Sth Australia
    redviper.. did you get those results from putting your data into genetic genie. The methylation side of things it gives a report on it under the results (thought I'd mention this as its easy to miss its there).
  3. redviper

    redviper

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    Hey Tania...

    Yep, I've been trying to make sense of all that information the best I can. So much to learn though. Wish I had paid more attention in science class!

    I also ran my results through Promethease this morning, which I must say is pretty good value for only $5
  4. taniaaust1

    taniaaust1 Senior Member

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    Sth Australia
    I'll comment on some of your detox ones as I have some the same so will cut and past the basic info I put together from a couple of sites on the ones I have as well. (this info below is a blend of info I cut and pasted from places with more complicated pieces left out, so I cant precisely reference it except mostly genetic genie info).

    SOD2

     
    Superoxide dismutase 2, mitochondrial



    also known as SOD2, is an enzyme which in humans is encoded by the SOD2 gene.


    This gene is a member of the iron/manganese
    superoxide dismutase family. It encodes a mitochondrial matrix protein that forms a homotetramer and binds one manganese ion per subunit. This protein transforms toxic superoxide, a byproduct of the mitochondrial electron transport chain, into hydrogen peroxide and diatomic oxygen.


    Mutations in this gene have been associated with
    idiopathiccardiomyopathy (IDC), sporadic motor neuron disease, and cancer. Mice lacking Sod2 die shortly after birth, indicating that unchecked levels of superoxide are incompatible with mammalian life.[3] However, mice 50% deficient in Sod2 have a normal lifespan and minimal phenotypic defects but do suffer increased DNA damage and increased incidence of cancer.[4]

    ................

    NAT2
    N-acetyltransferase 2 (arylamine N-acetyltransferase)

    is an enzyme which in humans is encoded by the NAT2 gene.[1]

    This gene encodes a type of N-acetyltransferase. The NAT2 isozyme functions to both activate and deactivate arylamine and hydrazine drugs and carcinogens. Polymorphisms in this gene are responsible for the N-acetylation polymorphism in which human populations segregate into rapid, intermediate, and slow acetylator phenotypes. Polymorphisms in NAT2 are also associated with higher incidences of cancer and drug toxicity. A second arylamine N-acetyltransferase gene (NAT1) is located near NAT2.[2]

    ........................

     
    GSTP1

     

    Glutathione S-transferase P

    is an
    enzyme that in humans is encoded by the GSTP1 gene.[1]HYPERLINK \l "cite_note-pmid7587384-2"[2]
    Glutathione S-transferases (GSTs) are a family of enzymes that play an important role in detoxification by catalyzing the conjugation of many hydrophobic and electrophilic compounds with reduced glutathione. Based on their biochemical, immunologic, and structural properties, the soluble GSTs are categorized into 4 main classes: alpha, mu, pi, and theta. The glutathione S-transferase pi gene (GSTP1) is a polymorphic gene encoding active, functionally different GSTP1 variant proteins that are thought to function in xenobiotic metabolism and play a role in susceptibility to cancer, and other diseases.[3]

    (note.. many pharma drugs are xenobiotic kind of drugs.. over 25% of pharma drugs are)

    ...........



    CYP1B1
     

    Cytochrome P450 1B1

    is an
    enzyme that in humans is encoded by the CYP1B1 gene.




    CYP1B1 belongs to the
    cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. The enzyme encoded by this gene localizes to the endoplasmic reticulum (ER) and metabolizes procarcinogens such as polycyclic aromatic hydrocarbons and 17beta-estradiol.




    CYP1B1 was not identified and sequenced until 1994. Recently CYP1B1 has been shown to be physiologically important in fetal development, since mutations in CYP1B1 are linked with a form of primary congenital glaucoma. It is thought that the enzyme also metabolizes a signaling molecule involved in eye development, possibly a steroid.


    CYP1B1 is regulated by the
    Aryl hydrocarbon receptor, a ligand activated transcription factor. It is part of the Phase I reactions in drug metabolism.


    .......................

    CYP2D6


     

    Cytochrome P450 2D6

    is an enzyme that in humans is encoded by the CYP2D6 gene. CYP2D6 is primarily expressed in the liver.
    CYP2D6 a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. In particular, CYP2D6 is responsible for the metabolism and elimination of approximately 25% of clinically used drugs.[1] This enzyme also metabolizes several endogenous substances such as hydroxytryptamines and neurosteroids.[1]

    There is considerable variation in the efficiency and amount of CYP2D6 enzyme produced between individuals. Hence for drugs that are metabolized by CYP2D6 (that is are CYP2D6 substrates), certain individuals will eliminate these drugs quickly (extensive metabolizers) while others slowly (poor metabolizers). If a drug is metabolized too quickly, it may decrease the drug's efficacy while if the drug is metabolized too slowly, toxicity may result.[2] Hence the dose of the drug may have to be adjusted to take into account of the speed at which it is metabolized by CYP2D6.[3]

    In addition, other drugs may function as inhibitors of CYP2D6 activity or inducers of CYP2D6 enzyme expression that will lead to decreased or increased CYP2D6 activity respectively. If such a drug is taken at the same time a second drug who is a CYP2D6 substrate, the first drug may affect the elimination rate of the second through what is known as a drug-drug interaction.[2]
     
    CYP2D6 shows the largest phenotypical variability among the CYPs, largely due to genetic polymorphism. The genotype accounts for normal, reduced, and non-existent CYP2D6 function in subjects.
    The CYP2D6 function in any particular subject may be described as one of the following:[5]
    poor metabolizer – little or no CYP2D6 function
    intermediate metabolizers – metabolize drugs at a rate somewhere between the poor and extensive metabolizers
    extensive metabolizer – normal CYP2D6 function
    ultrarapid metabolizer – multiple copies of the CYP2D6 gene are expressed, and therefore greater-than-normal CYP2D6 function
    ........

    Be aware that the ordinary wikipedia has some info the the various gene families too if you put in something like CYP2D6 etc. . www.genecards.org is a good place to look for info on various genes.
    Last edited: Nov 27, 2013
    Valentijn likes this.
  5. Graeme

    Graeme almost there...

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    Montreal
    Here's my detox profile. Does anything jump out at you guys? Is there any strategy I should implement? Thanks.


    Detox Profile Analysis

    CYP1A1*2C A4889G
    rs1048943
    TT
    -/-

    CYP1A1 m3 T3205C
    rs4986883
    TT
    -/-

    CYP1A1 C2453A
    rs1799814
    GG
    -/-

    CYP1A2 164A>C
    rs762551
    AC
    +/-

    CYP1B1 L432V
    rs1056836
    CG
    +/-

    CYP1B1 N453S
    rs1800440
    TT
    -/-

    CYP1B1 R48G
    rs10012
    CG
    +/-

    CYP2A6*2 1799T>A
    rs1801272
    AA
    -/-

    CYP2A6*20
    rs28399444
    II
    -/-

    CYP2C9*2 C430T
    rs1799853
    CC
    -/-

    CYP2C9*3 A1075C
    rs1057910
    AA
    -/-

    CYP2C19*17
    rs12248560
    CT
    +/-

    CYP2D6 S486T
    rs1135840
    CG
    +/-

    CYP2D6 100C>T
    rs1065852
    AG
    +/-

    CYP2D6 2850C>T
    rs16947
    GG
    -/-

    CYP2E1*1B 9896C>G
    rs2070676
    CC
    -/-

    CYP2E1*1B 10023G>A
    rs55897648
    GG
    -/-

    CYP2E1*4 4768G>A
    rs6413419
    GG
    -/-

    CYP3A4*1B
    rs2740574
    TT
    -/-

    CYP3A4*2 S222P
    rs55785340
    AA
    -/-

    CYP3A4*3 M445T
    rs4986910
    AA
    -/-

    CYP3A4*16 T185S
    rs12721627
    GG
    -/-

    GSTP1 I105V
    rs1695
    AA
    -/-

    GSTP1 A114V
    rs1138272
    CC
    -/-

    SOD2 A16V
    rs4880
    AG
    +/-

    NAT1 R187Q
    rs4986782
    GG
    -/-

    NAT1 R64W
    rs1805158
    CC
    -/-

    NAT2 I114T
    rs1801280
    CT
    +/-

    NAT2 R197Q
    rs1799930
    GG
    -/-

    NAT2 G286E
    rs1799931
    GG
    -/-

    NAT2 R64Q
    rs1801279
    GG
    -/-

    NAT2 K268R
    rs1208
    AG
    +/-
  6. redviper

    redviper

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    Thanks Tania, appreciate the info :)
  7. caledonia

    caledonia

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    Cincinnati, OH, USA
    Well my name in big letters in the title did do it's job and get my attention - lol. But in the future, if you want me or someone to respond, just type their name after an "@" like this @redviper, and they will get an alert message.

    You said you were male - technically, the MAO A should only have one +, because males only have one copy of the gene. But functionally, it's the same as having +/+, which I guess is why it shows up that way.

    You have one First Priority mutation, which is CBS A360A. That's the minor one, and I've never seen anyone with that mutation (outside of the Heartfixer) need to treat that. So it's probably safe to start with methyl supps, but if you do have problems, such as a stress/anxiety reaction, then you may have to go back and treat it.

    You have MTHFR C677T which affects folate, so some methylfolate for that. Several protocols also include folinic acid to help get around to the other side of the folate cycle to produce DNA and RNA bases. Some people may have trouble tolerating folinic acid supplementation. Technically, you should be able to convert methylfolate into folinic acid.

    You don't have any MTR or MTRR mutations, which are the ones that affect B12. In this case, I'm not sure if need B12 supplementation or not. It probably depends on how much methylfolate you're taking. It should be in the ratio of 5 parts B12 to 1 part methylfolate, or 5 part B12 to 3 parts methylfolate - with somewhat more B12 than folate, so you don't get into a methyl trapping situation.

    If you do decide to supplement with B12, for your COMT/VDR combo, you're somewhat sensitive, so Yasko suggests hydroxycobalamin and adenosylcobalamin. A few people (like me) have trouble with hydroxycobalamin despite their SNPs, so in that case, you would take methylcobalamin and adenosylcobalamin and just Start Low and Go Slow. Valentijn thinks that's due to the MTRR mutation, which I do have, and you don't, so you might be ok there.

    VDR Bsm is the Vitamin D Receptor, so get your Vit. D checked and if it's low, supplement for that.

    MAO A could affect mental health (serotonin). Yasko suggests not treating directly for that until the methylation cycle is working ok. Then she suggests some small sprinkles of 5htp (assuming you're not also taking an SSRI/SNRI).

    For the detox SNPs - the CYP1B1s can cause estrogen dominance which can cause estrogen related cancers (breast, prostate). The suggested strategy is to eat cruciferous veggies, or take DIM, IC3 or calcium deglucarate. Calcium deglucarate is the best if you have COMT and CBS mutations (which you do).

    CYP1A2 metabolizes various xenobiotics (chemicals), the most well known of which is caffeine. Those with mutations are slow detoxifiers, so caffeine would have a greater effect on you than a fast metabolizer like me.

    CYP2C9, CYP2D6, CYP2E1 affect the detoxification of various drugs, and may make you sensitive to them. Look at the Detoxigenomics link in my signature for a list of which drugs these are.

    GSTP affects glutathione. You will require more glutathione than average to overcome this. The best way to raise glutatione is via methylation treatment, not direct supplementation.

    SOD2 affects the mitochondria. You can supplement with supps containing GliSODin, or if you can't do gluten Biotec Extra Energy Enzymes. General mito support such as ribose, CoQ10, etc. may be helpful as well as resveratrol for oxidative stress.

    The NATs detoxify smoke and environmental chemicals. So don't smoke, avoid second hand smoke and paints, perfumes, etc. Many people with NATs are chemically sensitive.
    Beyond and Valentijn like this.
  8. caledonia

    caledonia

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    Cincinnati, OH, USA
    @Graeme

    Detox Profile Analysis

    CYP1A2 164A +/- slow caffeine metabolizer, so caffeine may wire you up more than others.

    CYP1B1 L432V +/- and CYP1B1 R48G +/- estrogen dominance possibly causing estrogen related cancers. Suggestions are cruciferous veggies, DIM, IC3 or calcium deglucarate.

    CYP2C19*17 +/-
    CYP2D6 S486T +/-
    CYP2D6 100C>T +/-
    Problems detoxifying various drugs. See the Detoxigenomics link in my signature below for more specific info.

    SOD2 A16V +/- Could affect the mitochondria. Suggest supps with GliSODin, or Biotec Extra Energy Enzymes if you can't do gluten. Mito supps such as ribose, CoQ10, etc, and resveratrol for oxidative stress.

    NAT2 I114T +/-
    NAT2 K268R +/-
    These detoxify smoke so don't smoke and stay away from second hand smoke. People with these can also be chemically sensitive, so avoid paints, perfumes, etc. if this is you.
    Last edited: Nov 28, 2013
    Graeme likes this.
  9. redviper

    redviper

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    Wow, thanks a lot Caledonia. I really appreciate it, everything you mentioned seems to align with what I've read so far on my SNP's.

    Now I'm going to take the opportunity to browse through the links in your signature page. Guess it's time to start learning all about Methylation :)
  10. Valentijn

    Valentijn Activity Level: 3

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    @redviper - I agree with what @caledonia said, except that I would doubt that MAOA needs to be treated. You have the slow version, but there's nothing wrong with that by itself. It just means that you break down neurotransmitters slower than some people do, but your VDR suggests that you also produce those neurotransmitters at a slower pace.

    So since you're likely slow on both creating and breaking down neurotransmitters, there's probably nothing there which requires treatment, especially if you don't have any related symptoms. If you were fast in producing neurotransmitters and slow in breaking them down, or slow in producing them and fast in breaking them down, then that might be more of an issue.
  11. Beyond

    Beyond 10% of discount in iHerb!--> PEZ915

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    Murcia, Spain
    Reading the post of caledonia made me want to add, regarding the validity/usefulness of 23andme, that I have been finding that these genetic tests are pretty useful. I have a very low blood level of vitamin D and "coincidentally" have the VDR homozigous mutation that predisposes you to that. Also, I am notoriously sensitive to air chemicals, fumes or the like and I have various NAT homo mutations. So some of these genes do in fact reflect real life outcomes.

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