Input on my 23andme results? What should I do next..

[mrsbond]

Here are my 23andme results on my methylation profile as ran through GG. I have done some functional testing (4-point saliva cortisol, UAA, UTM/UEE, comprehensive stool test) and I have been piecing together my own treatment over the last few months since I got my results. I have recently found a new practitioner who I *think* understands methylation/nutrigenomics and also my HEDS dx, however I have barely started seeing her and I would like to continue to learn from the smarties here

My biggest complaints right now are fatigue and muscle pain, poor sleep and gut issues..although I have started to see improvements in my gut by taking probiotics and addressing my candida overgrowth. I also tested myself for pyroluria and the results came back negative, however my blood work showed I am copper toxic and low ceruloplasmin and I have been working to balance that out as well.

Any input would be greatly appreciated! I appreciate you for taking the time to read through

+/+ COMT rV158M s4680 AA
+/+ COMT H62H rs4633 TT
+/+ VDR Taq rs731236 AA
+/- MAOA rs6323 GT
+/- MTHFR C677T rs1801133 AG
+/- MTHFR 03 rs2066470 AG
+/- MTHFR A1298C rs1801131 GT
+/+ MTRR A66G rs1801394 GG
+/+ MTRR A664A rs1802059 AA
+/- BHMT-02 rs567754 CT
+/+ BHMT-08 rs651852 TT
+/- CBS C699T rs234706 AG
+/- CBS A360A rs1801181 AG

 

[alicec]

There are threads on all those snps on PR - just do some searching.

 

[mrsbond]

Yes I have been researching all these SNP's the last 6 months or so, and I guess I am still a bit overwhelmed/confused and don't fully understand them and their relation to one another and thought maybe someone here would be able to explain it in a way that makes sense to me I also have been trying really hard to figure out how I can tell which SNP's are expressing based on my functional testing, but again I am at a loss still after all this time to find any markers on my testing to show me that. (I just realized I didn't upload my functional testing on my original post so I will go edit that right now and include them)

 

[alicec]

There is another thread going at the moment which may answer some of your questions - see here

Most of the snps you list are mentioned on that other thread and most have no impact.

+/+COMT V158M is a mis-sense mutation which does slow the enzyme produced by the gene to some extent. In itself it is likely to have only a modest effect.

In the other thread, I refer to a couple of posts I made about COMT. There is also a thread about it.

COMT snps may exert an effect on neurotransmitter balance but the idea that we can't tolerate methyl groups is a myth. You might be sensitive to methyl groups, but not particularly because of COMT.

+/- MTHFR C677T would also have a modest slowing of the enzyme produced by the gene, +/- MTHFR A1298C a very modest slowing. Yasko's claims about the latter snp affecting the backward reaction of the enzyme and subsequent BH4 recycling is just nonsense. The enzyme does neither of these things.

+/+ MTRR A66G would have a very modest slowing of the enzyme.

I also have been trying really hard to figure out how I can tell which SNP's are expressing based on my functional testing

Well if you have the snp it would be expressed, whether it has any impact is another question. Many snps have little or no impact, and for those that do, often the effect is quite small.

The functional assays you have done show the end-points of the interaction of many metabolic pathways. They may help to pinpoint functional deficiencies or metabolic blockages and so give some hints about which pathways are not working well. snps could at best be contributing factors to these problem.

 

[mrsbond]

Thank you! Yes I agree that about COMT and methyl donors because I recently started a fairly small dose of methyl b12 and methylfolate and seem to have no problems at all. However, I also have always been very sensitive to caffeine and even though I don't drink any caffeine anymore, when I used to I never drank it past 1 pm or it would take me even longer to fall asleep than normal.

That other thread has a lot of great info on it so I will continue to dig deep Also, I actually have 8 MTHFR +/- and have been working really hard to clean up my diet and my environment and I have started to notice the difference overall how I feel..especially with a clean diet. I think that may be the most important thing actually.

Regarding COMT and neurotransmitters, I did notice that on my MTHFRsupport report, my 'Neurotransmitter Pathway: Serotonin and Dopamine' section had a lot of red and yellows. If the COMT may have some effect on neurotransmitter balance and my neurotransmitter pathway is possibly impaired (due to the reds and yellows on MTHFRsupport), is it logical to assume I may have some neurotransmitter imbalance going on?

 

[alicec]

If the COMT may have some effect on neurotransmitter balance and my neurotransmitter pathway is possibly impaired (due to the reds and yellows on MTHFRsupport), is it logical to assume I may have some neurotransmitter imbalance going on?

That entirely depends on the actual snps and their combination. There is no shortcut to researching each of the snps individually. For some genes like COMT there is a lot of research, including defining haploblocks - certain combinations of snps which have an effect, even if the individual snps in the block do not. See this thread for info on two haploblocks as well as mis-sense COMT mutations.