MTHFR Gene Defect Survey of ME patients

ME patients: Do you have a defective methylenetetrahydrofolate reductase gene (determined by test)?


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gbells

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Survey on MTHFR gene mutations for ME patients.

The methylenetetrahydrofolate reductase (MTHFR) enzyme converts synthetic folic acid and dietary folate into its active form, L-methylfolate, which plays a critical role in neurotransmitter synthesis. Some individuals carry a mutation at the C677T SNP of the MTHFR gene, which results in a 35% reduction in activity for heterozygotes (C/T) and a 70% reduction in activity for homozygotes (T/T).1,2 Individuals who carry this mutation will have a reduced capacity to create L-methylfolate.
https://genesight.com/articles/is-t...n-for-patients-with-the-mthfr-c677t-mutation/
 
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nerd

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I certainly don't have the C677T mutation, but there is a huge chunk of the MTHFR gene missing despite the 30x sequencing. So I don't really know if it's a deletion or a gap. I don't think it's a deletion though, because it's just too large of a piece. I guess something affected the MTHFR in both saliva samples.
 

gbells

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Wow, 30% of the population has this but it is very prevalent in ME patients so far. I had no idea. EBV further decreases folate metabolism and it is important for nerve cells DNA repair, depression. B12 is also involved so this explains irritability and depression also. Perhaps the nerve hypersensitivity ME patients get is related to MTFHR and folate/B12 metabolism problems that are not being addressed by MDs. The MD I saw in 2012 did the gene test but didn't prescribe active B12 so I did not get any symptomatic benefit but when I supplemented both recently I noticed a big boost in my mood, aerobic capacity and mental energy.
 

Learner1

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Wow, 30% of the population has this but it is very prevalent in ME patients so far. I had no idea. EBV further decreases folate metabolism and it is important for nerve cells DNA repair, depression. B12 is also involved so this explains irritability and depression also. Perhaps the nerve hypersensitivity ME patients get is related to MTFHR and folate/B12 metabolism problems that are not being addressed by MDs. The MD I saw in 2012 did the gene test but didn't prescribe active B12 so I did not get any symptomatic benefit but when I supplemented both recently I noticed a big boost in my mood, aerobic capacity and mental energy.
Mutations are actually more common than that. Worth knowing one should only take 5-MTHF. However, other genes and, most importantly, environmental factors can dramatically change one's need for folate and other methylation nutrients.
 

pattismith

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"rs1801133 is a SNP that is relatively common and has been studied for (relatively) a long time. Also known as C677T, Ala222Val, and A222V"

"Homozygous rs1801133(T;T) individuals have ~30% of the expected MTHFR enzyme activity, and rs1801133(C;T) heterozygotes have ~65% activity, compared to the most common genotype, rs1801133(C;C)."
 

gbells

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Here's a statistic for the percentage of EBV in ME patients, 90%.

The seroprevalence of EBV in the general population and in CFS/ME patients is ~90%. And the proportion of CFS/ME patients with EBI2 upregulation was found to be between 38 and 55% CFS/ME patients, all of whom had IgG to EBV VCA.
(Kerr JR. Epstein-Barr Virus Induced Gene-2 Upregulation Identifies a Particular Subtype of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. Front Pediatr. 2019;7:59. Published 2019 Mar 13. doi:10.3389/fped.2019.00059)

Mutations are actually more common than that. Worth knowing one should only take 5-MTHF. However, other genes and, most importantly, environmental factors can dramatically change one's need for folate and other methylation nutrients.
Learner's comment raises the question whether EBV could give a false positive for MTHFR mutation by reading methylation instead of actual DNA sequences. The lab test is not for methylation of the gene but is for the actual bad gene itself so it does not give false positives. While EBV does impact the need for folate, increasing the severity of the effect for a heterozygous MTHFR patient, it isn't going to give a false positive as it doesn't actually code for the gene, it is impairing folate metabolism downstream.

Results typically are reported as negative or positive and, if positive, the report will name the mutation(s) present. Often, an interpretation of the results is also provided.

Only a small percentage of cases of elevated homocysteine are due to an inherited cause. Of these, MTHFR C677T and A1298C mutations are among the most common.

If a person has two copies (homozygous) of MTHFR C677T, or has one copy of C677T and one of A1298C, then it is likely that elevated homocysteine levels are due to these inherited mutations, or that the mutations are contributing to them.

Two copies of A1298C are not typically associated with increased homocysteine levels.

If the MTHFR mutation test is negative, then the C677T and A1298C mutations were not detected and the tested person's elevated homocysteine level is likely due to another cause. Other, more rare MTHFR genetic mutations will not be detected with typical testing.
https://labtestsonline.org/tests/mthfr-mutation#:~:text=The methylenetetrahydrofolate reductase (MTHFR) gene,, spina bifida, and others.

So the fact that we are seeing that MTFHR mutation predisposes people for ME is important and suggests a possible explanation why two similarly infected patients would give ME symptoms for one patient but not the other. This is also important when considering that the odds ratios of dying from cancer in ME patients are much higher. So the MTHFR mutation is likely increasing the cancer deaths as folate is important for DNA repair and we may lower cancer deaths in ME patients by getting these patients the activated folic acid they need to prevent early damaged cells from progressing to cancerous ones by having their DNA repaired.

Another factor would be whether the patient was able to develop protective antibodies that would limit the spread of infected cells. Here is where infection timing becomes important.

CFS was present in 0.5% of cancer cases overall and 0.5% of controls. CFS was associated with an increased risk of non-Hodgkin lymphoma (NHL) (OR = 1.29, 95% confidence interval [CI] = 1.16-1.43, P = 1.7 × 10−6). Among NHL subtypes, CFS was associated with diffuse large B cell lymphoma (OR = 1.34, 95% CI = 1.12-1.61), marginal zone lymphoma (OR = 1.88, 95% CI = 1.38-2.57), and B cell NHL not otherwise specified (OR = 1.51, 95% CI = 1.03-2.23). CFS associations with NHL overall and NHL subtypes remained elevated after excluding patients with medical conditions related to CFS or NHL, such as autoimmune conditions. CFS was also associated, although not after multiple comparison adjustment, with cancers of the pancreas (OR = 1.25, 95% CI = 1.07-1.47), kidney (OR = 1.27, 95% CI = 1.07-1.49), breast (OR = 0.85, 95% CI = 0.74-0.98), and oral cavity and pharynx (OR = 0.70, 95% CI = 0.49-1.00). Chronic immune activation or an infection associated with CFS may play a role in explaining the increased risk of NHL. Cancer 2012.
(Chiang, C. Chronic fatigue syndrome and subsequent risk of cancer among elderly US adults. December 2012Cancer 118(23))
 
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