23andme results - input appreciated!

[frenchmoxie]

Hi all, I received my 23andme results a few weeks ago and have been trying to learn as much as possible from the message boards. I would love to get some input on my results and see what you all think! (FYI results analyzed via genetic genie and Sterling’s site app.)

As far as treatment, I’ve started with SHMT spray (1 week ago) and every few days take one capsule of the Ultimate B Complex in addition to a trace mineral complex supplement (Seeking Health brand). Once things settle down a bit, I will then start with the Iron Related Bacterial Issues supplement … then onto CBS?

Also, urine essential element testing showed low levels of: Calcium, Cobalt, Molybdenum, Manganese, Selenium, Copper, and Sulfur. Urine Creatinine was at 932mg/24hr. (range: 600-1900)

Methylation - hetero

COMT V158M rs4680 AG +/-
COMT H62H rs4633 CT +/-
VDR Bsm rs1544410 CT +/-
VDR Taq rs731236 AG +/-
MTHFR A1298C rs1801131 GT +/-
MTHFR A1572G rs17367504 AG +/-
SHMT1 C1420T rs1979277 AG +/-
MAO-A R297R rs6323 GT +/-

BHMT-04 rs617219 AC +/-
BHMT-08 rs651852 CT +/-
BHMT R239Q rs3733890 AG +/-
CBS A13637G rs2851391 CT +/-
CBS A360A rs1801181 AG +/-
CBS C19150T rs4920037 AG +/-
CBS C699T rs234706 AG +/-
DAO rs2111902 GT +/-

MTHFD1 C105T rs1076991 CT +/-
MTHFD1 G1958A rs2236225 AG +/-
MTHFD1L rs6922269 AG +/-

Methylation - homozygous
MTRR A66G rs1801394 GG +/+
MTHFS rs6495446 CC +/+
DAO rs3741775 CC +/+
TCN2 C766G rs1801198 GG +/+

Detox – homozygous (will post hetero if anyone wants to see them)
CYP1B1 L432V rs1056836 CC +/+
CYP2C19*17 rs12248560 TT +/+
PON1 Q192R rs662 CC +/+

GSTT1 ABSENT (via genetic genie)?

 

[Valentijn]

Methylation - hetero

COMT V158M rs4680 AG +/-
COMT H62H rs4633 CT +/-
VDR Bsm rs1544410 CT +/-
VDR Taq rs731236 AG +/-
MTHFR A1298C rs1801131 GT +/-
MTHFR A1572G rs17367504 AG +/-
SHMT1 C1420T rs1979277 AG +/-
MAO-A R297R rs6323 GT +/-

BHMT-04 rs617219 AC +/-
BHMT-08 rs651852 CT +/-
BHMT R239Q rs3733890 AG +/-
CBS A13637G rs2851391 CT +/-
CBS A360A rs1801181 AG +/-
CBS C19150T rs4920037 AG +/-
CBS C699T rs234706 AG +/-


Methylation - homozygous
MTRR A66G rs1801394 GG +/+

MTHFR A1298C might result in methylfolate being slightly slower. But the A1573G only has research saying the G allele is tied into lower BP and less risk of hypertension, which I haven't seen strongly tied to methylation function, so I'd be wary about making any assumptions about that one.

MTRR A66G results in far less effectiveness in repairing MTR to be re-used. 3 to 4 times as much MTRR is needed. B12 might help with this.

COMT, MAOA, and VDR indicate you might be a bit slow in using up methyl groups, hence you might have trouble tolerating large amounts of them. Hence hydroxoB12 might be safer than methylB12, especially if taking high doses.

CBS and BHMT indicate you might be a bit slow in getting rid of homocysteine, which is associate with risk in numerous disease. B6 can help the slow version of CBS to work better.

SUMMARY:
B6 and methylfolate may be helpful, and B12 is probably needed.

 

[frenchmoxie]

CBS and BHMT indicate you might be a bit slow in getting rid of homocysteine, which is associate with risk in numerous disease. B6 can help the slow version of CBS to work better.

SUMMARY:
B6 and methylfolate may be helpful, and B12 is probably needed.

Thanks for the input! Do you have any ideas about Sulfur in regards to my results? I seem to feel horrible the day after eating anything in the Brassica family (collards, broccoli, and spinach). I'm assuming this is due to their high sulfur levels? Is this due to CBS mutations?

As far as CBS and BHMT go in regards to homocysteine, I've actually tested on the low end of normal for homocysteine. Any ideas about that?

 

[Valentijn]

Thanks for the input! Do you have any ideas about Sulfur in regards to my results? I seem to feel horrible the day after eating anything in the Brassica family (collards, broccoli, and spinach). I'm assuming this is due to their high sulfur levels? Is this due to CBS mutations?

None of the researched CBS mutations are capable of causing sulfur problems, but that's not to say there isn't something else going on. I'm -/- for C699T, but not exactly sulfur friendly myself

As far as CBS and BHMT go in regards to homocysteine, I've actually tested on the low end of normal for homocysteine. Any ideas about that?

None of the CBS or BHMT variations that you have are missense mutation. This means the structure of the protein created by the gene is unaltered, hence there's no big changes in function. While research does show the variations are relevant, the impact is quite small - in the neighborhood of a percentage point or two.

There are also other CBS and BHMT variations which might be having a bigger impact, though there's no easy geneticgenie program for sorting them yet. But you can search through your raw data if concerned about them:
http://forums.phoenixrising.me/index.php?threads/interesting-bhmt-and-bhmt2-variations.24512/
http://forums.phoenixrising.me/index.php?threads/interesting-cbs-variations.24492/

 

[frenchmoxie]

Valentijn:

I know I've still got a few more things to get in place before addressing MTRR A66G, but does this homozygous mutation mean that I'm not properly making methyl-B12 and that all of the hydroxy and adenosyl B12 I take isn't converted to the methyl B12 I need? At first I read the MTRR A66G had to do with RECYCLING of methlyB12, but now I'm reading that it gives me problems in FORMING methylB12? Is this correct?

And if that's the case... what is happening to the 50% of adenosylB12 that I'm ingesting that was supposed to be made into methylB12?

Thanks!

 

[Valentijn]

I know I've still got a few more things to get in place before addressing MTRR A66G, but does this homozygous mutation mean that I'm not properly making methyl-B12 and that all of the hydroxy and adenosyl B12 I take isn't converted to the methyl B12 I need? At first I read the MTRR A66G had to do with RECYCLING of methlyB12, but now I'm reading that it gives me problems in FORMING methylB12? Is this correct?

MTRR replenishes the cobalamin (B12) of MTR - its function is to recycle MTR by replenishing the B12 in it. From what I understand, MTR (and MTRR) is not directly involved in making methylcobalamin, merely in using it - though methionine produced by MTR is what results in methylation in general.

The general premise (by Yasko, Heartfixer, etc) seems to be that as long as enough methyl groups are present, there's never a problem in creating methylB12. And while methylB12 supplementation is the easiest and most direct way to deal with the problem, it can create nasty side effects in people who already have too many excess methyl groups due to slow COMT, MAOA, and VDR.

What MTRR A66G +/+ means is that the methionine synthase reductase which is produced is very inefficient at recycling MTR. B12 supplementation is supposed to help it do its job - if methylB12 works for you, then great, but if not, hydroxoB12 is a great alternative. And while your VDR and COMT variations might indicate some problems with excess methyl groups, the SNPs involved don't seem to be a very strong indicator.

 

[Crux]

Hi frenchmoxie;
A TCN++ means that there will be difficulty with B12 transport. That's why some folks must take high dosages.

With DAO++, Vitamin C, B6, and copper are needed if there is trouble metabolizing histamine.

 

[LynnD]

Crux,
What are the snp's that tell about histamine . IS that the DAO?
Am TCN rs1801198 GG , not sure what is risk allel in other TCN2
DAO rs3741775 CC. This is all interesting.
Thanks
Lynn D

 

[caledonia]

Thanks for the input! Do you have any ideas about Sulfur in regards to my results? I seem to feel horrible the day after eating anything in the Brassica family (collards, broccoli, and spinach). I'm assuming this is due to their high sulfur levels? Is this due to CBS mutations?

As far as CBS and BHMT go in regards to homocysteine, I've actually tested on the low end of normal for homocysteine. Any ideas about that?

If you read the Free Thiol page (link in my signature), problems with sulfur can be due to mercury being detoxified and released. Symptoms are depressed, tired, draggy, etc.

Low homocysteine can be a sign that CBS is expressed.

I'm not sure what to make of low sulfur. Sulfate should be high on urine sulfate strips. Maybe that's different from sulfur?

 

[Crux]

Crux,
What are the snp's that tell about histamine . IS that the DAO?
Am TCN rs1801198 GG , not sure what is risk allel in other TCN2
DAO rs3741775 CC. This is all interesting.
Thanks
Lynn D

Hi @LynnD ;

The more I look into snp analysis, the more confused I become!
DAO snps are associated with histamine metabolism, and some can be problematic when combined with other snps, like ones in the HNMT,HDC, and ABP1 snps, for instance.

When I look up DAO, rs 3741775, it is associated with bipolar disorder and schizophrenia, sometimes and sometimes not. So, now I still believe DAO snps are associatied with histamine intolerance, (HIT), but, rs 3741775 doesn't seem to be included.

I have this snp to, I'm also a CC, and I have had strong reactions to some histamine containing substances. ( especially red wine, although it has other allergens.) I've found that copper, in particular, helps. I do take vitamin C daily, and I did take B6, and sometimes p5p in the past. I get copper from foods, such as nuts, seeds, and dark chocolate.

http://www.ncbi.nlm.nih.gov/pubmed/21488903

http://ajcn.nutrition.org/content/85/5/1185.full

http://snpedia.com/index.php/Rs3741775

 

[Crux]

Hi All ;

snps in TCN2 are associated with transcobalamin deficiency,so if you have them, B12 can get stuck in the serum, and seem to be normal when tested. But it is not being bound and transported, so there's still a deficiency.

http://snpedia.com/index.php/Rs1801198

There are other TCN2 snps as well.

Edit:
It looks like the risk allele for rs 1801198 is C, not G. I keep finding some discrepancies from some of the analysis of livewello and mthfrsupport.com. I guess we'll need to compare their results to research.

snpedia has listed a few more snps in the TCN2, but I think there may be even more. Don't know where.

http://snpedia.com/index.php/TCN2

 

[Critterina]

Crux,
What are the snp's that tell about histamine . IS that the DAO?
Am TCN rs1801198 GG , not sure what is risk allel in other TCN2
DAO rs3741775 CC. This is all interesting.
Thanks
Lynn D

Hi LynnD,
DAO is one, HNMT is the other. DAO is the one that works in the gut, so if it's food-related histamine issues, it's DAO, at least partly.

Risk alleles I know about in DAO:
DAO 109277720 rs2070586 (A or G) A
DAO 109278747 rs2111902 (G or T) G
DAO 109283603 rs3741775 (A or C) C

Also, the minor allele of the following can be risky or protective (but I haven't looked up which is minor yet.)
risk rs2052129
risk rs2268999
risk rs10156191
risk rs1049742
protective rs2071514
protective rs1049748
protective rs2071517
low promo rs2052129


I think the above is from the following:
Association of single nucleotide polymorphisms in the diamine oxidase gene with diamine oxidase serum activities.
Maintz L, Yu CF, Rodríguez E, Baurecht H, Bieber T, Illig T, Weidinger S, Novak N.
Source
Department of Dermatology and Allergy, University of Bonn, Bonn, Germany.
Abstract
BACKGROUND:
Histamine intolerance (HIT) is associated with an excess of histamine because of an impaired function of the histamine-degrading enzyme diamine oxidase (DAO). The genetic background of HIT is unknown yet.
METHODS:
Case-control association study of all haplotype tagging and four previously reported DAO SNPs and one HNMT Single nucleotide polymorphism with symptoms of HIT and DAO serum activity in 484 German individuals including 285 patients with clinical symptoms of HIT and 199 controls.
RESULTS:
Diamine oxidase serum activity was significantly associated with seven SNPs within the DAO gene. The minor allele at rs2052129, rs2268999, rs10156191 and rs1049742 increased the risk for a reduced DAO activity whereas showing a moderate protective effect at rs2071514, rs1049748 and rs2071517 in the genotypic (P = 2.1 × 10(-8) , 7.6 × 10(-10) , 8.3 × 10(-10) , 0.009, 0.005, 0.00001, 0.006, respectively) and allelic genetic model (P = 2.5 × 10(-11) , 5.4 × 10(-13) , 8.9 × 10(-13) , 0.00002, 0.006, 0.0003, 0.005, respectively). Reporter gene assays at rs2052129 revealed a lower promoter activity (P = 0.016) of the minor allele. DAO mRNA expression in peripheral blood mononuclear cells of homozygous carriers of the minor allele at rs2052129, rs2268999, rs10156191 was lower (P = 0.002) than homozygous carriers of the major allele. Diamine oxidase variants were not associated with the HIT phenotype per se, only with DAO activity alone and the subgroup of HIT patients displaying a reduced DAO activity.
CONCLUSIONS:
DAO gene variants strongly influence DAO expression and activity but alone are not sufficient to fully effectuate the potentially associated disease state of HIT, suggesting an interplay of genetic and environmental factors.

 

[LynnD]

DAO is one, HNMT is the other. DAO is the one that works in the gut, so if it's food-related histamine issues, it's DAO, at least partly.

Risk alleles I know about in DAO:
DAO 109277720 rs2070586 (A or G) A
DAO 109278747 rs2111902 (G or T) G
DAO 109283603 rs3741775 (A or C) C

Also, the minor allele of the following can be risky or protective (but I haven't looked up which is minor yet.)
risk rs2052129
risk rs2268999
risk rs10156191
risk rs1049742
protective rs2071514
protective rs1049748
protective rs2071517
low promo rs2052129

I think if my low blood pressure is from histamine imbalance then had whole like, as gastro problems.

Am GG, TT and only risk is last DAO CC

GT, couldnt find next RS on 23 results,
TT, CT
no result, TT, GG, GT
will look HNMT later
Thank you
Lynn D

 

[musicchick581]

I'm DAO +/+ but how do we read the HNMT from 23 and me? It doesn't come up on Genetic Genie or on MTHFRSupport Variant. I see all the raw data but can't read it. I can't tell what the risk alleles are.
Also will taking DAO supplements help with DAO histamine responses?

 

[musicchick581]

Anyone?