Dissecting PN
Posted: Sat Nov 15, 2014 4:34 pm
Feeling that B12 is closely connected to my MS I connected with an ME/CFS forum where b12 is a HUGE topic of discussion. I met this Ozzie (PhD Bio-Chem) that has a new B12 transdermal oils co. He offered to review my genetic profile which I sent him. His review (highlights):
Hi PN,
I have done your snps and attach the file.
Green is good (-/-), red is bad (+/+).
Generally I don't take that much notice to yellow (+/-), as normally about 50% of people have yellow (25% green).
There are a couple of problems with the snp analysis. If you have more than one snp in a particular gene you cannot tell if the snps are all on one copy of the protein produced, or spread across both copies of the protein.
You have quite a few snps in the folate cycle, notable is
MTHFDIL rs1076991 +/+
MTHFR rs13306561 +/+ and an odd GG at rs1801133
MTHFS rs6495446 +/+
Now the combination of the mutations is additive, and will make it very hard for you to process folate unless you have high levels of dietary or supplement folate.
It also means that you are going to sacrifice both 5MTHF and methylB12 in order to make SAM for methylation.
Methylation via SAM has been shown to be essential for short term memory, loss of which is characteristic of MS.
You have a bunch of mutations associated with break-down of neurotransmitters. Now these can do two things, they can make you very hypersensitive to external stimuli, or alternatively they can lead to eventual down-regulation of the neuronal/synpase activity.
COMT rs4633 +/+
DAO rs1049742 +/+
MAO rs6323 +/+ rs5906883 +/+
You also have problems in the methylating enzymes
PEMT rs4646406 +/+. This is responsible for both the synthesis of Phosphoryl choline and is also used the synthesis of adrenalin from nor-adrenalin.
You have two sets of mutations in cystathione B-synthase, the first enzyme in the conversion of homocysteine to glutathione.
rs2851391 +/+, rs4633 +/+
This mutation alone can lead to increased homocysteine. High levels of homocysteine are often seen in MS and have been put forward as one of the causes of MS. Elevated plasma homocysteine levels have been reported in patients with MS and associated with male gender.
Elevated homocysteine is also seen in folate and vitamin B12 deficiency.
You have mutations in your eNOS gene
rs2918188 +/+
eNOS is responsible for opening up your blood vessels.
The last mutation of significance is in your VDR taq +/+.
The VDR is responsible for uptake and processing of vitamin D. Mutations in the genes normally mean that you have to keep your vitamin D intake high. Vitamin D, whilst often associated with osteoporosis, is also very important for mitochondrial function and nerve growth.
Low vitamin D is causally related to the development of MS, and there has recently been a study correlating the use of high block sunscreen and the development of MS in Denmark. (you probably already know this).
You will notice quite a few of your mutations are associated with proteins that use FAD/FMN, including DAO, MAO, MTHFR, MTRR, NOS, PEMT, TYMS. This generally means that you have to keep your riboflavin (B2) levels up high and you have to make sure that you have a properly functioning thyroid. This is needed to convert riboflavin to FAD and FMN.
Now this may be of relevance in the development of MS, as there is a "use it or lose it" rule for neuronal synapses. If you stop a nerve from firing if it fires too much will eventually stop the neuron from firing.
The reason that I mentioned your ACE mutation because some of the symptoms of AD are similar to MS and also some of the brain changes seen in the two conditions are similar. You are the only person that we have done with MS so far, so I don't know if this is a common pattern.
In general your pattern of snps looks quite simlar to that seen with CFS and ASD.
We know that we have had good success with high dose B1, B2 (particularly), B3, B9 and folate supplementation along with Ado/Me B12 and also high dose vitamin D3 (above 3000 IU/day).
I have quite a file on VB12 deficiency and MS, which I attach.
Please let me know if there is further that we can help you with.
It would be helpful if we could now marry your genetics to your current B12 deficiency symptoms at http://b12oils.com/deficiencyfrm.htm
We don't currently have an MS form. Symptomology can help in defining which system is caused by which enzyme.
Best wishes,
G
Hi PN,
I have done your snps and attach the file.
Green is good (-/-), red is bad (+/+).
Generally I don't take that much notice to yellow (+/-), as normally about 50% of people have yellow (25% green).
There are a couple of problems with the snp analysis. If you have more than one snp in a particular gene you cannot tell if the snps are all on one copy of the protein produced, or spread across both copies of the protein.
You have quite a few snps in the folate cycle, notable is
MTHFDIL rs1076991 +/+
MTHFR rs13306561 +/+ and an odd GG at rs1801133
MTHFS rs6495446 +/+
Now the combination of the mutations is additive, and will make it very hard for you to process folate unless you have high levels of dietary or supplement folate.
It also means that you are going to sacrifice both 5MTHF and methylB12 in order to make SAM for methylation.
Methylation via SAM has been shown to be essential for short term memory, loss of which is characteristic of MS.
You have a bunch of mutations associated with break-down of neurotransmitters. Now these can do two things, they can make you very hypersensitive to external stimuli, or alternatively they can lead to eventual down-regulation of the neuronal/synpase activity.
COMT rs4633 +/+
DAO rs1049742 +/+
MAO rs6323 +/+ rs5906883 +/+
You also have problems in the methylating enzymes
PEMT rs4646406 +/+. This is responsible for both the synthesis of Phosphoryl choline and is also used the synthesis of adrenalin from nor-adrenalin.
You have two sets of mutations in cystathione B-synthase, the first enzyme in the conversion of homocysteine to glutathione.
rs2851391 +/+, rs4633 +/+
This mutation alone can lead to increased homocysteine. High levels of homocysteine are often seen in MS and have been put forward as one of the causes of MS. Elevated plasma homocysteine levels have been reported in patients with MS and associated with male gender.
Elevated homocysteine is also seen in folate and vitamin B12 deficiency.
You have mutations in your eNOS gene
rs2918188 +/+
eNOS is responsible for opening up your blood vessels.
The last mutation of significance is in your VDR taq +/+.
The VDR is responsible for uptake and processing of vitamin D. Mutations in the genes normally mean that you have to keep your vitamin D intake high. Vitamin D, whilst often associated with osteoporosis, is also very important for mitochondrial function and nerve growth.
Low vitamin D is causally related to the development of MS, and there has recently been a study correlating the use of high block sunscreen and the development of MS in Denmark. (you probably already know this).
You will notice quite a few of your mutations are associated with proteins that use FAD/FMN, including DAO, MAO, MTHFR, MTRR, NOS, PEMT, TYMS. This generally means that you have to keep your riboflavin (B2) levels up high and you have to make sure that you have a properly functioning thyroid. This is needed to convert riboflavin to FAD and FMN.
Now this may be of relevance in the development of MS, as there is a "use it or lose it" rule for neuronal synapses. If you stop a nerve from firing if it fires too much will eventually stop the neuron from firing.
The reason that I mentioned your ACE mutation because some of the symptoms of AD are similar to MS and also some of the brain changes seen in the two conditions are similar. You are the only person that we have done with MS so far, so I don't know if this is a common pattern.
In general your pattern of snps looks quite simlar to that seen with CFS and ASD.
We know that we have had good success with high dose B1, B2 (particularly), B3, B9 and folate supplementation along with Ado/Me B12 and also high dose vitamin D3 (above 3000 IU/day).
I have quite a file on VB12 deficiency and MS, which I attach.
Please let me know if there is further that we can help you with.
It would be helpful if we could now marry your genetics to your current B12 deficiency symptoms at http://b12oils.com/deficiencyfrm.htm
We don't currently have an MS form. Symptomology can help in defining which system is caused by which enzyme.
Best wishes,
G