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Help me with my 23andme results - compared to detoxigenomics

Thinktank

Senior Member
Messages
1,640
Location
Europe
I finally received my 23andme results yesterday and ran the methylation report and detox report on geneticgenie with the raw data.

One thing that really bothers me is the difference between 23andme and genova detoxigenomic result on my SOD2 gene. On the 23andme result it shows as -/- while detoxigenomics is +/+. Who's right, who's wrong?

Anyway, here are my results. Hope to hear some recommendations.

23andme + geneticgenie methylation profile
Gene & Variation rsID Alleles Result
COMT V158M rs4680 GG -/-
COMT H62H rs4633 CC -/-
COMT P199P rs769224 GG -/-
VDR Bsm rs1544410 CT +/-
VDR Taq rs731236 AG +/-
MAO-A R297R rs6323 GG -/-
ACAT1-02 rs3741049 GG -/-
MTHFR C677T rs1801133 AG +/-
MTHFR 03 P39P rs2066470 AG +/-
MTHFR A1298C rs1801131 GT +/-
MTR A2756G rs1805087 AA -/-
MTRR A66G rs1801394 AG +/-
MTRR H595Y rs10380 CC -/-
MTRR K350A rs162036 AA -/-
MTRR R415T rs2287780 CC -/-
MTRR A664A rs1802059 AG +/-
BHMT-02 rs567754 CT +/-
BHMT-04 rs617219 AC +/-
BHMT-08 rs651852 CT +/-
AHCY-01 rs819147 TT -/-
AHCY-02 rs819134 AA -/-
AHCY-19 rs819171 TT -/-
CBS C699T rs234706 GG -/-
CBS A360A rs1801181 GG -/-
CBS N212N rs2298758 GG -/-
SHMT1 C1420T rs1979277 AG +/-


23andme Genova detoxigenomics
Gene & Variation rsID Alleles Result Result
CYP1A1*2C A4889G rs1048943 TT -/- NO polymorphims on CYP1A1 / not sure which variation is tested
CYP1A1 m3 T3205C rs4986883 TT -/- NO polymorphims on CYP1A1 / not sure which variation is tested
CYP1A1 C2453A rs1799814 GG -/- NO polymorphims on CYP1A1 / not sure which variation is tested
CYP1A2 164A>C rs762551 AC +/- Not included in genova detoxigenomics
CYP1B1 L432V rs1056836 GG +/+ NO polymorphims on CYP1B1 / not sure which variation is tested
CYP1B1 N453S rs1800440 TT -/- NO polymorphims on CYP1B1 / not sure which variation is tested
CYP1B1 R48G rs10012 CG +/- NO polymorphims on CYP1B1 / not sure which variation is tested
CYP2A6*2 1799T>A rs1801272 AA -/- NO polymorphims on CYP2A6 / not sure which variation is tested
CYP2A6*20 rs28399444 II -/- NO polymorphims on CYP2A6 / not sure which variation is tested
CYP2C9*2 C430T rs1799853 CT +/- Polymorphism detected for CYP2C9 / not sure which variation is tested
CYP2C9*3 A1075C rs1057910 AA -/- Polymorphism detected for CYP2C9 / not sure which variation is tested
CYP2C19*17 rs12248560 CC -/- NO polymorphims on CYP2C19 / not sure which variation is tested
CYP2D6 S486T rs1135840 CG +/- NO polymorphims on CYP2D6 / not sure which variation is tested
CYP2D6 100C>T rs1065852 AG +/- NO polymorphims on CYP2D6 / not sure which variation is tested
CYP2D6 2850C>T rs16947 GG -/- NO polymorphims on CYP2D6 / not sure which variation is tested
CYP2E1*1B 9896C>G rs2070676 CC -/- Polymorphism detected for CYP2E1 / not sure which variation is tested
CYP2E1*1B 10023G>A rs55897648 GG -/- Polymorphism detected for CYP2E1 / not sure which variation is tested
CYP2E1*4 4768G>A rs6413419 GG -/- Polymorphism detected for CYP2E1 / not sure which variation is tested
CYP3A4*1B rs2740574 TT -/- NO polymorphims on CYP3A4 / not sure which variation is tested
CYP3A4*2 S222P rs55785340 AA -/- NO polymorphims on CYP3A4 / not sure which variation is tested
CYP3A4*3 M445T rs4986910 AA -/- NO polymorphims on CYP3A4 / not sure which variation is tested
CYP3A4*16 T185S rs12721627 GG -/- NO polymorphims on CYP3A4 / not sure which variation is tested
GSTP1 I105V rs1695 AG +/- +/-
GSTP1 A114V rs1138272 CT +/- +/-
SOD2 A16V rs4880 AA -/- +/+
NAT1 R187Q rs4986782 GG -/- -/-
NAT1 R64W rs1805158 CC -/- -/-
NAT2 I114T rs1801280 CT +/- +/-
NAT2 R197Q rs1799930 AG +/- +/-
NAT2 G286E rs1799931 GG -/- -/-
NAT2 R64Q rs1801279 GG -/- -/-
NAT2 K268R rs1208 AG +/- +/-

Gene Result Result
GSTT1 Absent* maybe absent
 

Sea

Senior Member
Messages
1,286
Location
NSW Australia
I'm not sure what you mean by saying 23andme result is -/-
23andme don't report like that. They report your alleles for particular snps.

Genetic Genie takes your raw data from 23andme for the snps that Yasko tests and tells you the risk alleles according to Yasko. It has nothing to do with 23andme

Genetic Genie, following Yasko's ideas, calls the G allele (or C on the negative strand) for SOD2 A16V the risk allele. This doesn't fit with any of the research which shows that the A allele (or T on the negative strand) is associated with various risks and a 30 - 40% slower function.

G = Alanine
A = Valine

So Genetic Genie, Yasko, Detoxigenomics and 23andme all agree on your alleles for this snp. The disagreement is in which one is the risk.

Who's right? I'd go with the weight of the research that says you have the riskier version
 
Messages
15,786
VDR Bsm rs1544410 CT +/-
MTHFR C677T rs1801133 AG +/-
MTHFR 03 P39P rs2066470 AG +/-
MTHFR A1298C rs1801131 GT +/-
MTRR A66G rs1801394 AG +/-
MTRR A664A rs1802059 AG +/-
BHMT-08 rs651852 CT +/-
CBS C699T rs234706 GG -/-
SHMT1 C1420T rs1979277 AG +/-
Gene Result Result
GSTT1 Absent* maybe absent
Heterozygous MTHFR C677T indicates that folate production is at 65% of normal. Combined with heterozygous MTHFR A1298C, this can indicate that folate production is even lower, at 30% of normal. SHMT1 can aggravate this as well. Methylfolate supplementation is probably needed.

MTRR A66G has a pretty big effect with homozygous, so may have a smaller effect when heterozygous, and A664A has a minor effect as well. B12 supplementation may help. Because you have the faster versions of COMT and MAOA, you might have no problems with methyl groups, hence methylB12 might work fine for you and is the easier form of B12 to buy.

BHMT-08 and CBS C699T can indicate slower disposal of homocysteine, which is associated with increased risk factors for various disease. If this is the case, B6 supplementation can help in decreasing homocysteine levels via the CBS route.

GSTT1 is a gene which uses glutathione for certain functions. It's used in some types of detoxification, and missing the gene means you have a harder time dealing with certain toxins. Hence there's a greater risk of cancer, and a greater risk of liver damage from certain medications. Rituximab, for example, may be contraindicated. I haven't looked into the specific drugs which might be problematic yet, though I probably should since I'm missing the same gene :D At any rate, it may help to avoid pollutants and other environmental toxins, and take it easy with pharmaceutical drugs or anything else which can impact the liver.
 

Thinktank

Senior Member
Messages
1,640
Location
Europe
Sea, i still have a lot of reading to do on this whole genetic testing and methylation.
By -/- i mean the outcome from running the raw 23andme data through geneticgenie, which then reports -/-.

Valentijn, thanks for your input.
I have L-methylfolate 1000mcg from Life extension. Is that a too high dose to start with?
Also have methylcobalmin sublingual spray somewhere laying around but the dose is probably too high to start with at 500mcg - 8333%.
How much p5p should i start with? I used it years ago when i was still "healthy" and into fitness, it gave me very vivid dreams and it also helped me with energy. I have p5p from source natural @ 100mg.

In February my B12 was 912 (after intramuscular shots), in late July it had dropped to 512 and i guess it's even lower now.
Folic acid was in the medium range.
Homocysteine borderline high
Vit. D 43 (after loads of sun exposure), usually it's between 22 - 25. Maybe i should supplement with vitamin D again because of the VDR heterozygous mutation.

I have inflammatory bowel disease so i probably don't absorb enough B12 and folate from food. That and the genetic factor is a good reason to supplement with B12 and folate. I guess my whole methylation cycle is messed up as well.
I just have to find some forms that my intestines can tolerate. I react badly to most medications and vitamins, especially B-complexes. I have to figure out if it's just one of the B-vitamins or a combination thereof.
From single high dosages i have noticed:
B1: overstimulation but no crash
B2: My intestines don't like it, Big D and very frequent orange urination.
B3: Flush and big D. No experience with niacinamide yet.
B5 / panthetine: No effect
B6: Overstimulation, vivid dreams
Biotin: Makes me tired
B12 (methylcobalmin spray): A bit of overstimulation
CDP choline: No effect or a bit tired

About the GSTT1 gene, i'm quite sensitive to chemicals and toxins, i can't stand cigarette smoke and other fumes.

Nutreval plasma showed borderline low glutathione and Nutreval urine showed a normal glutathione level.
My liver is already damaged :), MRI, CT and PET/CT shows innumerable small lesions of just a few mm in size, they have no idea what causes or caused it but i believe it's due to lyme's or some co-infection.

As i told you before in a private message i'm going to have my neurotransmitters and methylation factors tested with the Dutch laboratory. I'll post the results next month.

Offtopic: I just made a list of all the supplements i have. In the last 1 and half year i have bought over 150 supplements which of more than half is still unopened lol.
 
Messages
15,786
I have L-methylfolate 1000mcg from Life extension. Is that a too high dose to start with?
Also have methylcobalmin sublingual spray somewhere laying around but the dose is probably too high to start with at 500mcg - 8333%.
How much p5p should i start with? I used it years ago when i was still "healthy" and into fitness, it gave me very vivid dreams and it also helped me with energy. I have p5p from source natural @ 100mg.
Your spray is a lower dose than the 1000mcg from Life Extension, so might be better to try that first. But 1000mcg isn't super high either, though it might be best to start with one of those every day or two until you know how you'll react.

For B6 100mg is at the maximum recommended dose (absent certain disease). It produces some toxins as it breaks down, which ME/CFS patients might have more trouble dealing with than most people, hence a lower dose might be a good idea. I think a doctor recommended I take no more than 50mg per day, and I seem to be okay with that.

In February my B12 was 912 (after intramuscular shots), in late July it had dropped to 512 and i guess it's even lower now.
Folic acid was in the medium range.
Homocysteine borderline high
Folic acid testing isn't really helpful in determining folate levels. Folic acid is the inactive form, and that's what you have trouble converting into the active form. Because most tests don't distinguish between forms, there's no way to know that your folate isn't low, and the high levels might just be due to high levels of folic acid which you can't use.

Vit. D 43 (after loads of sun exposure), usually it's between 22 - 25. Maybe i should supplement with vitamin D again because of the VDR heterozygous mutation.
VDR Bsm doesn't have a big impact, but there may be other VDR or vitamin D problems elsewhere. Some additional 23andMe VDR mutations are listed at http://forums.phoenixrising.me/index.php?threads/interesting-vdr-variations.24480/


My liver is already damaged :), MRI, CT and PET/CT shows innumerable small lesions of just a few mm in size, they have no idea what causes or caused it but i believe it's due to lyme's or some co-infection.
The damage could be due to your GSTT1 and/or related detoxing problems. Hence you might want to be very careful about drugs and dosages, especially with things known to have toxic byproducts, like B6 and NSAIDs, etc.
 

Thinktank

Senior Member
Messages
1,640
Location
Europe
Your spray is a lower dose than the 1000mcg from Life Extension, so might be better to try that first. But 1000mcg isn't super high either, though it might be best to start with one of those every day or two until you know how you'll react.

I will do that. Although not sure if i should start with the methylation support now or after testing by KDM next month.

For B6 100mg is at the maximum recommended dose (absent certain disease). It produces some toxins as it breaks down, which ME/CFS patients might have more trouble dealing with than most people, hence a lower dose might be a good idea. I think a doctor recommended I take no more than 50mg per day, and I seem to be okay with that.
Which toxins are you referring to? I'll try a lower dose P5P.

Folic acid testing isn't really helpful in determining folate levels. Folic acid is the inactive form, and that's what you have trouble converting into the active form. Because most tests don't distinguish between forms, there's no way to know that your folate isn't low, and the high levels might just be due to high levels of folic acid which you can't use.
Yeah i figured that out, i tried to explain that prior to knowing my MTHFR mutations to my Dr. but she didn't know what i was talking about and insisted me to take the prescribed folic acid which i refused.
So measuring folate levels is not possible?

VDR Bsm doesn't have a big impact, but there may be other VDR or vitamin D problems elsewhere. Some additional 23andMe VDR mutations are listed at http://forums.phoenixrising.me/index.php?threads/interesting-vdr-variations.24480/
Thanks, i'll check it out. My Vitamin D is usually chronically low if i don't supplement with vitamin D.
But when supplementing with vitamin D i usually get a very messed up feeling. The only vitamin D that i seem to have tolerated so far is the 50k D prescription vitamin from the hospital, to be taken once weekly.http://forums.phoenixrising.me/index.php?threads/interesting-vdr-variations.24480/


http://forums.phoenixrising.me/index.php?threads/interesting-vdr-variations.24480/
The damage could be due to your GSTT1 and/or related detoxing problems. Hence you might want to be very careful about drugs and dosages, especially with things known to have toxic byproducts, like B6 and NSAIDs, etc.
That's for sure, i have serious detox problems. Anyway, thanks again for your support and i will start reading on the various methylation protocols.
Which one is your favorite?
I guess the best place to start is reading the info from Rich, Freddd, heartfixer, yasko and Dr. Lynch. Then based on my genetic and other results start a custom methylation protocol. It sounds like a huge puzzle to figure out because there's now just so much going on in my body i don't know where or when to start. If i would just have visited and done KDM's testing earlier....
 

Critterina

Senior Member
Messages
1,238
Location
Arizona, USA
If you're going to do a set protocol before you figure out your specialized one, I'll tell you what I like: I like Freddd's if you can tolerate the methylcobalamin, I like Rich's SMP if you can't. I think you'll be able to, based on your SNPs.

Then you will experiment on yourself and tailor, probably based on symptoms as much as SNPs. I have trouble only making one change at at time, but I encourage other to do so. I would definitely read up and then tailor to suit yourself. For example, I use the "Energy will falter" recipe for supplements from Heartfixer that's under the CBS entry - even though I know the CBS concept is wrong the way it's explained on Heartfixer; the energy remedy has been helpful to me.
 

caledonia

Senior Member
COMT V158M rs4680 GG -/-
COMT H62H rs4633 CC -/-
COMT P199P rs769224 GG -/-
VDR Bsm rs1544410 CT +/-
VDR Taq rs731236 AG +/-
MAO-A R297R rs6323 GG -/-
ACAT1-02 rs3741049 GG -/-
MTHFR C677T rs1801133 AG +/-
MTHFR 03 P39P rs2066470 AG +/-
MTHFR A1298C rs1801131 GT +/-
MTR A2756G rs1805087 AA -/-
MTRR A66G rs1801394 AG +/-
MTRR H595Y rs10380 CC -/-
MTRR K350A rs162036 AA -/-
MTRR R415T rs2287780 CC -/-
MTRR A664A rs1802059 AG +/-
BHMT-02 rs567754 CT +/-
BHMT-04 rs617219 AC +/-
BHMT-08 rs651852 CT +/-
AHCY-01 rs819147 TT -/-
AHCY-02 rs819134 AA -/-
AHCY-19 rs819171 TT -/-
CBS C699T rs234706 GG -/-
CBS A360A rs1801181 GG -/-
CBS N212N rs2298758 GG -/-
SHMT1 C1420T rs1979277 AG +/-

You have one First Priority mutation, which is SHMT. That's one of the "leaky gut genes". People with that gene can have gut problems. You reported inflammatory bowel disease. The idea is to treat the gut at the same time as treating the SHMT SNP, which is supposed to have a better outcome than not treating them together. For SHMT take folinic acid. For the gut, get some stool testing, then if indicated, do a 4R gut rebuilding program (kill off bad bugs, replace the good bacteria, repair the gut lining). This should put you in a much better position for tolerating and absorbing supplements. It may take several months to get that fixed.

Then getting into the core of methylation - definitely some methylfolate for MTHFRs.

You have two MTRRs, which is B12 recycling, so likely some B12 for that. With your COMT/VDR combination, Yasko suggests hydroxycobalamin, adenosylcobalamin and also methylcobalamin, but less of it.

You have all the BHMTs, which is the secondary shortcut methylation pathway, so some TMG and phosphatidyl serine for that.

More tomorrow on the detox SNPs, if I can remember.
 

caledonia

Senior Member
I finally received my 23andme results yesterday and ran the methylation report and detox report on geneticgenie with the raw data.

One thing that really bothers me is the difference between 23andme and genova detoxigenomic result on my SOD2 gene. On the 23andme result it shows as -/- while detoxigenomics is +/+. Who's right, who's wrong?

If Genova is a blood test, I would go with that over the 23andme saliva test. There is supposed to be a 3% error rate for saliva.

The other thing is maybe it comes out with the same alleles on both, but the interpretation is different. There appears to be some controversy over which is the risk allele.

http://www.snpedia.com/index.php/Rs4880

There appears to be some conflict in the literature over the effect of this SNP. Having a valine at codon 16 is said to reduce enzyme activity [PMID 15864132], and thus lead to increased oxidative stress, yet in at least one study of the actual enzyme levels measured in people, SOD2 activity was 33% higher in (C;T) or (T;T) individuals compared to (C;C) individuals [PMID 16538174].

There are two different naming systems meaning the same thing. A=T and C=G
So rs4880 AA is the same as saying rs4880 TT.
 

caledonia

Senior Member
CYP1A2 164A>C rs762551 AC +/- Not included in genova detoxigenomics
CYP1B1 L432V rs1056836 GG +/+ NO polymorphims on CYP1B1 / not sure which variation is tested
CYP1B1 R48G rs10012 CG +/- NO polymorphims on CYP1B1 / not sure which variation is tested
CYP2C9*2 C430T rs1799853 CT +/- Polymorphism detected for CYP2C9 / not sure which variation is tested
CYP2C9*3 A1075C rs1057910 AA -/- Polymorphism detected for CYP2C9 / not sure which variation is tested
CYP2D6 S486T rs1135840 CG +/- NO polymorphims on CYP2D6 / not sure which variation is tested
CYP2D6 100C>T rs1065852 AG +/- NO polymorphims on CYP2D6 / not sure which variation is tested
CYP2E1*1B 9896C>G rs2070676 CC -/- Polymorphism detected for CYP2E1 / not sure which variation is tested
CYP2E1*1B 10023G>A rs55897648 GG -/- Polymorphism detected for CYP2E1 / not sure which variation is tested
CYP2E1*4 4768G>A rs6413419 GG -/- Polymorphism detected for CYP2E1 / not sure which variation is tested
GSTP1 I105V rs1695 AG +/- +/-
GSTP1 A114V rs1138272 CT +/- +/-
SOD2 A16V rs4880 AA -/- +/+
NAT2 I114T rs1801280 CT +/- +/-
NAT2 R197Q rs1799930 AG +/- +/-
NAT2 K268R rs1208 AG +/- +/-

I'll just go over each one you're + for regardless of which test it showed up on.

CYP1A2 - actually I think this is a typo and should read CYP1A1.

MTHFRsupport says: CYP1A1 and CYP1B1 breakdown estrogen into estradiol and esterone, which gets broken down into 2 hydroxy esterone, 4 hydroxy esterone, and 6 hydroxy esterone. 2 hydroxy estrone is a good one, the 4 and 16 will bind onto estrogen receptors and cause estrogen related cancers such as breast and uterine or prostate. CYP1B1 breaks down into 4 and 16 hydroxy esterone. So - mutations cause estrogen dominance. There are some supps for this - IC3, DIM or calcium deglucarate. Calcium deglucarate is supposed to be better for those with CBS. You can also eat cruciferous vegetables.

Detoxigenomics says:
(CYP1A1) detoxifies polycyclic aromatic hydrocarbons (PAHs) produced from the combustion of organic
materials (exhaust fumes,charbroiled meats, etc.) So avoid those.
(CYP2C9) detoxifies coumadin® and sulfonylureas. A risk allele means you could have more trouble with these medicines and may need lower doses.
(CYP2D6) detoxifies ~20% of all prescription drugs including tricyclics, MAOIs, SSRIs, opiates, anti-arrhythmics, beta- blockers, Cimetidine, etc. A risk allele means you could have more trouble with these medicines and may need lower doses.
(CYP2E1) detoxifies nitrosamines and ethanol (acetaldehyde). Risk allele means trouble detoxifying.
GSTP - MTHFRsupport says:
reception site for glutathione. If you have this mutation you need more than the average amount of glutathione production.

GSTP - Detoxigenomics says: Defects in GST activity can contribute to fatigue syndromes, and to various cancers throughout the body. Glutathione-S-transferase detoxifies many water-soluble environmental toxins, including many solvents, herbicides, fungicides, lipid peroxides, and heavy metals (e.g.,mercury, cadmium, and lead). The various forms of GST work together to eliminate toxins. Decreased glutathione conjugation capacity may increase toxic burden and increase oxidative stress.

SOD2 - MTHFRsupport says:
People with this can have problems with even the tiniest amount of methyl folate, because methyl folate increases nitric oxide. The byproduct of nitric oxide is peroxynitrate. People with SOD2 can't handle the peroxy nitrate well and so will have an adverse reaction to methyl folate. Treatment for SOD2–get the methylation cycle working so you can raise glutathione. Certain mushrooms and herbs. GlipiSOD. (Also on the Phoenix rising forum we've discussed Extra Energy Enzymes which got someone out of bed and which are gluten-free.

SOD2 - Detoxigenomics says: SOD2 is present in the mitochondria. Changes in the SOD enzyme are associated with changes in risk for neurodegenerative disorders like ALS. Superoxide Dismutase is an enzyme that protects cells from increased oxidative stress and free radical damage to cell structures like membranes, mitochondria, DNA, and protein.
NAT - MTHFRsupport says:
NAT1, NAT2–controls breakdown of certain drugs and the acetylation pathway in the liver. NAT detoxifies petrochemicals. People with NAT problems can be chemically sensitive to perfume gasoline toluene xylene etc.–multiple chemical sensitivity. Vitamin B5 can help with this, however, those with CBS can have problems with this vitamin as it contains sulfur.

NAT - Detoxigenomics says: N-acetyl Transferase detoxifies many environmental toxins, including tobacco smoke and exhaust fumes. Polymorphisms can result in slower than normal or faster than normal addition of an acetyl group to these toxins. Slow acetylators have a build up of toxins in the system and rapid acetylators add acetyl groups so rapidly that they make mistakes in the process. Both slow and rapid acetylators are at increased risk for toxic overload if they are exposed to environmental toxins. If the toxin exposure is reduced, the risk is reduced.

=-==-=-=-==-

So in terms of the detox SNPs causing or adding to ME/CFS and treatment for that, GSTP and SOD2 are the worst ones. Treatment for GSTP would be raising glutathione via methylation treatment. Treatment for SOD2 was discussed above.

The other SNPs would have an impact, in that if you encounter the various toxins which you have trouble detoxifying and then are also low in glutathione to begin with, it would make you more susceptible to glutathione depletion and a partial methylation block, and thus ME/CFS. So avoiding or minimizing those toxins will always be a good practice for you.

Doing supps or cruciferous veggies for estrogen dominance would just be a good general health practice to hopefully avoid cancers.
 

Journeyman

Senior Member
Messages
193
Heterozygous MTHFR C677T indicates that folate production is at 65% of normal. Combined with heterozygous MTHFR A1298C, this can indicate that folate production is even lower, at 30% of normal. SHMT1 can aggravate this as well. Methylfolate supplementation is probably needed.

MTRR A66G has a pretty big effect with homozygous, so may have a smaller effect when heterozygous, and A664A has a minor effect as well. B12 supplementation may help. Because you have the faster versions of COMT and MAOA, you might have no problems with methyl groups, hence methylB12 might work fine for you and is the easier form of B12 to buy.

BHMT-08 and CBS C699T can indicate slower disposal of homocysteine, which is associated with increased risk factors for various disease. If this is the case, B6 supplementation can help in decreasing homocysteine levels via the CBS route.

GSTT1 is a gene which uses glutathione for certain functions. It's used in some types of detoxification, and missing the gene means you have a harder time dealing with certain toxins. Hence there's a greater risk of cancer, and a greater risk of liver damage from certain medications. Rituximab, for example, may be contraindicated. I haven't looked into the specific drugs which might be problematic yet, though I probably should since I'm missing the same gene :D At any rate, it may help to avoid pollutants and other environmental toxins, and take it easy with pharmaceutical drugs or anything else which can impact the liver.

What a great help Valentijn: even as someone whose got a basic understanding of the SNP's and what mutations mean for bodily function I found little info that would guide me on what sort of dosages might be relevant to someone with my specific mutations. Now I know (thanks to your info in this reply) that my bodies effective folate production is probably 25-30% of the normal amount due to the heterozygous MTHFR C677T and MTHFR A1298C I possess. I also have heterozygous SHMT1 so perhaps I'm running at 15-20% effective folate production? I'm always impressed at the knowledge and support provided in these forums....
 

Journeyman

Senior Member
Messages
193
I'm not sure what you mean by saying 23andme result is -/-
23andme don't report like that. They report your alleles for particular snps.

Genetic Genie takes your raw data from 23andme for the snps that Yasko tests and tells you the risk alleles according to Yasko. It has nothing to do with 23andme

Genetic Genie, following Yasko's ideas, calls the G allele (or C on the negative strand) for SOD2 A16V the risk allele. This doesn't fit with any of the research which shows that the A allele (or T on the negative strand) is associated with various risks and a 30 - 40% slower function.

G = Alanine
A = Valine

So Genetic Genie, Yasko, Detoxigenomics and 23andme all agree on your alleles for this snp. The disagreement is in which one is the risk.

Who's right? I'd go with the weight of the research that says you have the riskier version

Like ThinkTank I also have the SOD2 mutation (though mine is heterozygous) and so I read this reply with great interest. Sea: how did you become so knowledgeable about the SNP's and the specific strands/allele's? do you have a scientific background? PS - why is there uncertainty over which allele combo is actually the 'underfunctioning' gene so we can actually know where we all stand on the SOD2 which having read other parts of this thread: is actually important for anyone considering decent folate supplementation.
 
Messages
15,786
Now I know (thanks to your info in this reply) that my bodies effective folate production is probably 25-30% of the normal amount due to the heterozygous MTHFR C677T and MTHFR A1298C I possess.
Actually it's slightly trickier than that. The A1298C only knocks things down further if the mutation is on the opposite strand versus your C677T mutation. So you could be at 65% or 30%, depending on whether you got both mutations from the same parent, or one mutation from each parent. There's no way to tell from 23andMe results, because they report the results in alphabetical order, instead of doing one strand first and then the other.
 

Sea

Senior Member
Messages
1,286
Location
NSW Australia
Like ThinkTank I also have the SOD2 mutation (though mine is heterozygous) and so I read this reply with great interest. Sea: how did you become so knowledgeable about the SNP's and the specific strands/allele's? do you have a scientific background? PS - why is there uncertainty over which allele combo is actually the 'underfunctioning' gene so we can actually know where we all stand on the SOD2 which having read other parts of this thread: is actually important for anyone considering decent folate supplementation.

I'm not really very knowledgeable, I've just done lots of research in order to help my health. A year ago I knew little about genetics and nothing about snps. My background is teaching and I like to understand how and why things are.

Often one allele can confer a risk for something (say cancer) but the other allele gives a risk for something else. It becomes tricky then to be definitive but at least research usually agrees on a specific allele for a specific risk.

There is a lot of controversy over the SODA16V snp and research hasn't really yet provided a great deal of clarification as papers have been published showing one allele to be a risk factor for something and then follow up papers have shown the opposite. As Caledonia linked different research has shown the opposite alleles to have greater or lesser enzyme activity.

There will be uncertainty until the different outcomes can be explained. Obviously there is more influencing the outcome than just the snp to have such differing results.

This is one I am still researching. Interestingly one of the papers I read had a greater risk for one particular thing in the heterozygous version of this snp than either of the homozygous versions. That is a very unusual outcome.

I think particularly when we discuss this snp we need to share our alleles (or the protein they code for) rather than say I have this mutation or I have the risky version because
1. There is disagreement on whether the change is A - V or V - A
2. There is disagreement on which allele is the risk for anything in particular
 

Thinktank

Senior Member
Messages
1,640
Location
Europe
caledonia
Thanks for the helpful info.
I've been on a 4R-ish program for the last 6 months under supervision of a functional practicioner. Unfortunately it has not helped much yet and i even had a few crashes / IBD flares because the underlying cause of my gastrointestinal symptoms might be little bit more complex than outlined by the 4R program. It's very likely i have lyme's.
I've been diagnosed with Crohn's but the findings are way too unspecific.

About stool testing, already did the CDSA 2.0, leaky gut and extensive candida profile from genova and will receive the results of my GI effects profile next week.

I'm to see Dr. KDM within 2 weeks so i'm holding off any supplementation until then because i don't want anything to influence the outcome of the testing.

Among other testing i will do within a few weeks is a methylation panel and genova's organic acids or re-do the nutreval test. I think it's a good idea to check the current methylation status and combine that with the genetic results.
 

Sea

Senior Member
Messages
1,286
Location
NSW Australia
Genetic Genie takes your raw data from 23andme for the snps that Yasko tests and tells you the risk alleles according to Yasko.

Genetic Genie, following Yasko's ideas, calls the G allele (or C on the negative strand) for SOD2 A16V the risk allele.

Just to make some corrections since I can't go back and edit my earlier post. I can't actually find anywhere that Yasko mentions SOD2. The methylation panel follows Yasko's ideas. I thought the detox profile did too but apparently not. I'm not sure where the detox profile snps come from, maybe Genovations?

This doesn't fit with any of the research which shows that the A allele (or T on the negative strand) is associated with various risks and a 30 - 40% slower function.

G = Alanine
A = Valine

Actually having looked further there's some research both ways. It really isn't clear exactly what effect this snp has
 

caledonia

Senior Member
Just to make some corrections since I can't go back and edit my earlier post. I can't actually find anywhere that Yasko mentions SOD2. The methylation panel follows Yasko's ideas. I thought the detox profile did too but apparently not. I'm not sure where the detox profile snps come from, maybe Genovations?

The detox SNPs come from the Genova Detoxigenomics test, not Yasko. There is a link in my signature.
 

Journeyman

Senior Member
Messages
193
I'm not really very knowledgeable, I've just done lots of research in order to help my health. A year ago I knew little about genetics and nothing about snps. My background is teaching and I like to understand how and why things are.

Often one allele can confer a risk for something (say cancer) but the other allele gives a risk for something else. It becomes tricky then to be definitive but at least research usually agrees on a specific allele for a specific risk.

There is a lot of controversy over the SODA16V snp and research hasn't really yet provided a great deal of clarification as papers have been published showing one allele to be a risk factor for something and then follow up papers have shown the opposite. As Caledonia linked different research has shown the opposite alleles to have greater or lesser enzyme activity.

There will be uncertainty until the different outcomes can be explained. Obviously there is more influencing the outcome than just the snp to have such differing results.

This is one I am still researching. Interestingly one of the papers I read had a greater risk for one particular thing in the heterozygous version of this snp than either of the homozygous versions. That is a very unusual outcome.

I think particularly when we discuss this snp we need to share our alleles (or the protein they code for) rather than say I have this mutation or I have the risky version because
1. There is disagreement on whether the change is A - V or V - A
2. There is disagreement on which allele is the risk for anything in particular

The more I look into this field the more i realise just how cutting edge and new it is. In a few years time when (hopefully) the mainstream public realises the importance of understanding their own genes/weaknesses then standardised nomenclature and consistent understandings will be reached. In the meantime we should all work towards that using your clear logical approach methinks! WD