My 23andMe results. Could anyone help decypher my Genetic Genie results?

[Antares in NYC]

So I finally went for it and did the 23andMe genetic testing. Very interesting results, some very surprising, like the fact that I have 3.0% Neanderthal DNA. I've noticed that many of us have high percentages of Neanderthal DNA; wonder if it would be worth looking into that in light of our condition.

Anyway, I did run the raw data from 23andMe through the Genetic Genie, and got the attached results. Could anyone kindly interpret these for me? Having a hard time understanding what this all means:

Gene & Variationrs ID Alleles Result
COMT V158M rs4680 AG +/-
COMT H62H rs4633 CT +/-
COMT P199P rs769224 GG -/-
VDR Bsm rs1544410 CT +/-
VDR Taq rs731236 AG +/-
MAO A R297R rs6323 T +/+
ACAT1-02 rs3741049 GG -/-
MTHFR C677T rs1801133 AG +/-
MTHFR 03 P39P rs2066470 GG -/-
MTHFR A1298C rs1801131 GT +/-
MTR A2756G rs1805087 AG +/-
MTRR A66G rs1801394 AG +/-
MTRR H595Y not found n/a n/a
MTRR K350A rs162036 AA -/-
MTRR R415Tnot found n/a n/a
MTRR A664A rs1802059 AG +/-
BHMT-02 rs567754 CT +/-
BHMT-04 not found n/a n/a
BHMT-08 rs651852 CT +/-
AHCY-01 rs819147 TT -/-
AHCY-02 not found n/a n/a
AHCY-19 rs819171 TT -/-
CBS C699T rs234706 GG -/-
CBS A360A rs1801181 AA +/+
CBS N212N not found n/a n/a
SHMT1 C1420T not found n/a n/a

 

[taniaaust1]

I can see one issue which certainly should be treated. You are "compound heterozgous" as far as the MTHFR mutation genes go. This causes a 50% loss of function in that area. So that is like having a double copy of MTHFR.

www.mthfrsupport.com.au/what-is-mthfr/
"
There are currently a total of 34 mutations in the MTHFR.
The MTHFR gene sits on Chromosome 1. There are two key variants we test for (as at this stage there is little or no research on the others).

• • MTHFR C677T
  • MTHFR A1298C

Heterozygous = 1 copy of the gene from either parent
Homozygous = 1 copy of the gene from each parent
MTHFR C677T Heterozygous = 40% loss of function *
MTHFR C677T Homozygous = 70% loss of function *
MTHFR A1298C Heterozygous = 20% loss of function (research not known)
MTHFR A1298C Homozygous = between 50-70% **
MTHFR C677T & MTHFR A1298C heterozygous = compound heterozygous = 50% loss of function
"

 

[taniaaust1]

Here's some info on some of your detox stuff from my own past research into some things. (note none of the links will work)

"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]
"
..............

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.[1]
CYP1B1 is regulated by the Aryl hydrocarbon receptor, a ligand activated transcription factor. It is part of the Phase I reactions in drug metabolism.
........

NAT2
N-acetyltransferase 2 (arylamine N-acetyltransferase)
, also known as NAT2, 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]

..........

I suggest seeing you had a double copy of a NAT2 mutation, to research the one you have and find out what drugs cause issues in this group, so you are more aware of which may be dangerous to you. Some drugs to some mutations can be life threatening eg one of the mutations I have (I forget now which.. this?? or another of my mutations??) certain anti-virals can cause life threatening reactions and are best avoided.

 

[caledonia]

COMT V158M rs4680 AG +/-
VDR Bsm rs1544410 CT +/-
VDR Taq rs731236 AG +/-
MAO A R297R rs6323 T +/+
MTHFR C677T rs1801133 AG +/-
MTHFR A1298C rs1801131 GT +/-
MTR A2756G rs1805087 AG +/-
MTRR A66G rs1801394 AG +/-
MTRR A664A rs1802059 AG +/-
BHMT-02 rs567754 CT +/-
BHMT-04 not found n/a n/a
BHMT-08 rs651852 CT +/-
CBS A360A rs1801181 AA +/+
SHMT1 C1420T not found n/a n/a

You have one First Priority mutation, which is CBS A360A. This one is not a problem for most people, but you also have some BHMTs so that can add to CBS. Go to the Heartfixer page for more info on how to tell if CBS is expressed and if you need to do a CBS protocol.

SHMT is a no call. If you have leaky gut issues, especially if you have a hard time getting them resolved you might have SHMT. Treatment is simply to get some folinic acid.

You have both MTHFR mutations, so some methylfolate for that.

YOu have both MTR (b12 intake) and MTRR (B12 recycling) which is the B12 double whammy. So some B12 for that.

For your COMT/VDR combo Yasko suggests Hydroxycobalamin and Adenosylcobalamin.

For the BHMTs which is the secondary methylation cycle, some sunflower lecithin which will convert to TMG.

For MAO A, if after the rest of the cycle is balanced and you're still experiencing mental health type problems Yasko suggests sprinkles of 5htp. This is contraindicated if you're also on an SSRI/SNRI.

More on detox later.

 

[caledonia]

Detox SNPs

CYP1A1 - detoxifies aromatic hydrocarbons such as car exhaust and charbroiled meats. It is suggested to avoid those.
CYP1B1 - can cause estrogen dominance which can cause estrogen related cancers such as breast, cervical, or prostate in males. It is suggested to eat cruciferous veggies to lower estrogen. If your estrogen is high you can also supplement with DIM, IC3 (components in the cruciferous veggies), or if CBS is an issue, calcium d glucarate.
CYP2D6 - detoxifies 20% of all prescription drugs including psych drugs and beta blockers. May have trouble tolerating those.
SOD2 A16V - affects the mitochondria. You can do SOD supplementation such as GliSODin or Biotech Extra Energy ezmymes. Or you can do mito supplementation, such as ribose, carnitine, CoQ10, etc. That approach worked best for me.
NAT2 - detoxifies smoke. Don't smoke and avoid second hand smoke.

The general advice for detox SNPs is to eat your fruits and veggies and avoid toxins.

 

[Antares in NYC]

Here's some info on some of your detox stuff from my own past research into some things. (note none of the links will work)

"SOD2
Superoxide dismutase 2, mitochondrial
, also known as SOD2, is an
enzyme which in humans is encoded by the SOD2 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.
........

NAT2
N-acetyltransferase 2 (arylamine N-acetyltransferase)
, also known as NAT2, is an enzyme which in humans is encoded by the NAT2 gene.[1]
..........

I suggest seeing you had a double copy of a NAT2 mutation, to research the one you have and find out what drugs cause issues in this group, so you are more aware of which may be dangerous to you. Some drugs to some mutations can be life threatening eg one of the mutations I have (I forget now which.. this?? or another of my mutations??) certain anti-virals can cause life threatening reactions and are best avoided.

Hi Tania,

Thanks so much for the info. Considering the dangers of the three mutations you pointed, in addition to the MTHFR issues is there anything I can do to counter them? Is there a way to treat or (possibly) reverse these mutations? I'm definitely worried, and wondering how much of this genetic stuff is related to my relentless CFS symptoms.

 

[Antares in NYC]

You have one First Priority mutation, which is CBS A360A. This one is not a problem for most people, but you also have some BHMTs so that can add to CBS. Go to the Heartfixer page for more info on how to tell if CBS is expressed and if you need to do a CBS protocol.

Caledonia,
Thanks for the wealth of information on my genetic profile. I'm trying to learn about this stuff, little by little, but still find most of it confusing. I couldn't find the CBS protocol from Heartfixer. Do you have any other sources to research if I need a CBS protocol? One thing that rings true here is how extremely sensitive I am to sulfur-based medicines. They give me extreme allergic reactions requiring steroids and sometimes even hospitalization.

SHMT is a no call. If you have leaky gut issues, especially if you have a hard time getting them resolved you might have SHMT. Treatment is simply to get some folinic acid.

I do have MAJOR leaky gut issues. Several colonoscopies, endoscopies, and thousands of dollars later, no gastro doctor can figure out why.

You have both MTHFR mutations, so some methylfolate for that.
You have both MTR (b12 intake) and MTRR (B12 recycling) which is the B12 double whammy. So some B12 for that.

I have already been taking B12 because of my severe B12 deficiency. I have not noticed any improvement since I started taking B12 on a refgular basis for more than a year, but I suspect that the other mutations may be draining all my energy, wasting these B12 shots.

 

[caledonia]

Caledonia,
Thanks for the wealth of information on my genetic profile. I'm trying to learn about this stuff, little by little, but still find most of it confusing. I couldn't find the CBS protocol from Heartfixer. Do you have any other sources to research if I need a CBS protocol? One thing that rings true here is how extremely sensitive I am to sulfur-based medicines. They give me extreme allergic reactions requiring steroids and sometimes even hospitalization.

Go to the Heartfixer page here: http://www.heartfixer.com/AMRI-Nutrigenomics.htm
Scroll past the methylation diagram. You will see a list of links in large letters. Click on the two CBS links (the second and third links in the list). This will give you all the info about CBS and it's treatment.

I do have MAJOR leaky gut issues. Several colonoscopies, endoscopies, and thousands of dollars later, no gastro doctor can figure out why.

Leaky gut is caused by bad gut bugs such as candida. You can't look at the stomach and intestines with a camera and see candida, which is obviously on the microscopic level. A gastro doc is not the right kind of doc to find or fix leaky gut. You need a naturopath or functional medicine doctor. The 4R Gut Rebuilding Program I have listed in my links is the same program used by the Functional Medicine Institute which trains functional medicine doctors.

I have already been taking B12 because of my severe B12 deficiency. I have not noticed any improvement since I started taking B12 on a refgular basis for more than a year, but I suspect that the other mutations may be draining all my energy, wasting these B12 shots.

You may not notice any improvement if you also need methylfolate. You need BOTH methylfolate and B12 to make methyl groups, which will restart methylation. It's like mixing baking soda and vinegar. If you just have some baking soda, there is no reaction. If you just have vinegar, there is no reaction. If you mix them both together - Bam!

Another possible problem could be lack of lithium, which helps B12 transport. Or the wrong form or type of B12. There may be other reasons. I have all these listed in Roadblocks to Successful Methylation, in my signature links.

 

[Antares in NYC]

Here's my major confusion about these protocols:

- Some researchers place a great importance on the CBS mutation (Yasko, etc), while others claim that the effects of CBS mutations are greatly exaggerated. Are we close to a consensus on this matter?

- For me, in addition to the MTHFR and MTR mutations, there's something about the CBS mutations that rings familiar: as I became progressively ill with ME/CFS, I became less and less tolerant of sulfur and sulfa-based medications. It has gotten so bad that today, a single dose of tetracycline or doxy would send me to the hospital with horrible hives and dangerous anaphylactic reactions. Soemthing rings true there: the more my CFS progressed, the more intolerant I became of sulfur.

- I checked the protocols for CBS mutations and got overwhelmed. That protocol is extremely restrictive with foods. Extremely! I'm already on a gluten-free diet to help starve the Lyme; if I add the protocol for CBS, I really don't know what I'll be able to ingest other than air and water. Seriously don't know what to do here.

- Two weeks ago I started the simplified methylation protocol by Rich Van Konynenburg. At what point would you start noticing a difference? I know it's been just two weeks, but like everyone else in these boards, I'm really sick of feeling so sick all the time after 15 years dealing with this. Any general indication of when you would start noticing any improvements with methylation?

Thanks in advance, folks.

 

[Helen]

....- Two weeks ago I started the simplified methylation protocol by Rich Van Konynenburg. At what point would you start noticing a difference? I know it's been just two weeks, but like everyone else in these boards, I'm really sick of feeling so sick all the time after 15 years dealing with this. Any general indication of when you would start noticing any improvements with methylation?....

If you need B12 and get an injection with MeCbl you might notice an effect in some hours. With a severe deficiency you would need injections and with your MTHFR mutations you need folate supplementation too.

There is no consensus about the need to start with a CBS protocol. Konynenburg and Nathan found in their clinical study that noone needed that - and they cooperated with Yasko to treat those that didn´t get enough well initially.

 

[Valentijn]

- Some researchers place a great importance on the CBS mutation (Yasko, etc), while others claim that the effects of CBS mutations are greatly exaggerated. Are we close to a consensus on this matter?

There is absolutely no research even remotely supporting the claims by Yasko about CBS SNPs. Her claims seem to be based on a huge misinterpretation of a study where half of the CBS gene was removed in a lab yeast, and some wild theories based on problems present in Downs' Syndrome patients who have three copies of the CBS gene.

How she got from "half the gene missing or 3 copies of it causes serious malfunction" to "a extremely common and very small up-regulation in a single SNP causes serious malfunction" is a complete mystery. Luckily for those who prefer mystery and borderline hysteria over science, Yasko sells expensive solutions for the problem

So - 0 evidence for SNP-based claims regarding CBS, and several strongly contradictory indications.

However, some people might conceivably have up-regulation of the CBS gene due to external factors. Many anecdotally report that the "treatment" for CBS is helpful. But whether or not they find that treatment helpful seems to be unrelated to CBS SNP status ... maybe @caledonia or others are aware of common indications of CBS (or sulfur) problems.

Also be aware that the CBS protocol is aimed at increasing homocysteine. This is generally considered a very bad idea, unless homocysteine levels are known to be too low, as elevated homocysteine is associated with increased risk of some potentially deadly diseases. Down-regulating the CBS gene is also very likely to result in reduced production of glutathione, which most would also consider to be a not-very-good thing to do.

 

[caledonia]

- I checked the protocols for CBS mutations and got overwhelmed. That protocol is extremely restrictive with foods. Extremely! I'm already on a gluten-free diet to help starve the Lyme; if I add the protocol for CBS, I really don't know what I'll be able to ingest other than air and water. Seriously don't know what to do here.

- Two weeks ago I started the simplified methylation protocol by Rich Van Konynenburg. At what point would you start noticing a difference? I know it's been just two weeks, but like everyone else in these boards, I'm really sick of feeling so sick all the time after 15 years dealing with this. Any general indication of when you would start noticing any improvements with methylation?

Thanks in advance, folks.

If you decide to do the CBS protocol, try using the Free Thiol diet instead of the Low Sulfur diet. Free Thiols are supposed to be more important than sulfur per se. I was able to do the CBS protocol successfully using this diet (see the link in my signature). I only had to restrict 4 foods and no meat. Note that the CBS protocol is only temporary - like a few months.

There is a honeymoon period for getting methylation restarted. Rich was mentioned 6-8 weeks with his protocol. It would also depend on if you're taking full amounts or not. I'm taking extremely tiny amounts and it was more like three months. Actually what I noticed was not feeling better, but feeling worse with potassium deficiency indicating healing was going on and my need for potassium was increased to help with healing.

Once I figured that out and started potassium supplementation, then I started noticing various benefits.

 

[caledonia]

If you need B12 and get an injection with MeCbl you might notice an effect in some hours. With a severe deficiency you would need injections and with your MTHFR mutations you need folate supplementation too.

There is no consensus about the need to start with a CBS protocol. Konynenburg and Nathan found in their clinical study that noone needed that - and they cooperated with Yasko to treat those that didn´t get enough well initially.

Rich hypothesized that you could bypass treating CBS if you started very low and very gradually increased. This was not my experience however. I was still having problems with even 1 mcg of methylcobalamin. Therefore, I ended up doing the CBS protocol, which resolved the problem.

 

[caledonia]

@Antares in NYC, try reading my document Roadblocks to Successful Methylation (linked in my signature). I have complete CBS info there.

I know that there are problems with Yasko's explanation of CBS, but anecdotally, CBS treatment worked for me.