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POLL: What MTHFR mutations do you have?

What MTHFR mutations do you have?


  • Total voters
    42

Gingergrrl

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@drob31 My new CFS doctor told me that 30% of regular population has these mutations but about 95% of the CFS population has them. I am compound heterozygous and assumed that is what he meant?
 

Valentijn

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For ME 12 patients I currently have easily accessible data for, at C677T (rs1801133) there 8 "A" alleles out of 24, which is 33.3%. Expected prevalence of the "A" allele in the general population is 32.5%, so we're dead normal. The controls have 9 "A" alleles out of 24, so it's slightly more common in the controls than the ME patients.

For A1298C (rs1801131) the ME patients and the controls each have 6 "G" allels out of 24, so 25%. Expected prevalence in the general population is 22.8%. So again, we're completely normal.

I don't believe the (Yasko?) claims that we have a huge incidence of those mutations in the ME/CFS population.
 

drob31

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Someone selected Compound Homozygous C677T and A1298C. I know that's really rare. I was more interested in the breakdown of MTHFR mutations versus if they had one or didn't have one.
 

Valentijn

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Someone selected Compound Homozygous C677T and A1298C. I know that's really rare. I was more interested in the breakdown of MTHFR mutations versus if they had one or didn't have one.
If C677T is already homozygous, then the status of A1298C is insignificant.
 

Valentijn

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Here's the 23andMe data I have for the SNPs which Yasko tests for, for 18 ME patients and 18 controls matched by maternal haplogroup (as an approximation of ethnicity). The Yasko SNPs where everyone has exactly the same version as each other are excluded (2 SNPs), as well as duplicate SNPs where everyone has the same result for multiple SNPs (3 SNPs).

Missense mutations are in bold red underlined font. The cell colors reflect how Yasko flags them. Included in the "Diff" columns is the difference between each group (patients or controls) and the closest prevalence results (patients or controls or general population MAF).

Yasko_Methylation.gif

So while there is some variation for ME patients compared to controls and the general population, it's quite small ... alleles of only 3 SNPs are around 10% more common in ME patients. Whereas the controls have several SNPs where they have 15-20% increased prevalence of minor alleles.

The most interesting increase for ME patients would be the number of people with homozygous MTHFR C677T or potentially compound heterozygous status with MTHFR A1298C. 5 ME patients are homozygous for C677T, compared to 1 control. 2 ME patients are potentially compound heterozygous for C677T and A1298C and 3 controls are potentially compound heterozygous. Because 23andMe doesn't indicate if the two mutations are on different strands, there's only a 50/50 chance of compound heterozygous status for those who are heterozygous for both SNPs. Hence 5-7 ME patients have MTHFR function reduced to 30%, compared to 1-4 controls.

But on the flip side, we have more patients with no MTHFR impact, compared with controls. Hence the controls have at least 11 members with 65% functionality of MTHFR, versus 5 ME patients. Hence the small difference of only 9% in overall minor allele prevalence at C677T.

So there might be a small increase in the prevalence of significant MTHFR mutations among ME patients. But it's much smaller than the claims of 40-75% increased prevalence, etc. And due to the small sample size, the differences shown above probably aren't statistically significant. Hence these results might be indicative of a modest but significant difference which could be verified in a larger sample, or it might just be a false positive - random luck of the draw.
 
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drob31

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@drob31 My new CFS doctor told me that 30% of regular population has these mutations but about 95% of the CFS population has them. I am compound heterozygous and assumed that is what he meant?

According to Valentijn, there isn't much a statistical difference. I guess my poll is lacking allot of data without the "none" option.
 

drob31

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Here's the 23andMe data I have for the SNPs which Yasko tests for, for 18 ME patients and 18 controls matched by maternal haplogroup (as an approximation of ethnicity). The Yasko SNPs where everyone has exactly the same version as each other are excluded (2 SNPs), as well as duplicate SNPs where everyone has the same result for multiple SNPs (3 SNPs).

.


So, according to your data MTHFR isn't the right place to look. I guess if someone wanted to cover all aspects, however, they could still take the supplements for MTHFR, but while investigating other areas.
 

Valentijn

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So, according to your data MTHFR isn't the right place to look. I guess if someone wanted to cover all aspects, however, they could still take the supplements for MTHFR, but while investigating other areas.
It's possible that there are MTHFR SNPs which aren't tested by 23andMe that are having an impact. It's also possible that other genes involved with folate or B12 are malfunctioning in different places for different ME patients.

But those are just possibilities - the data which I currently have access to simply doesn't support the possibility of MTHFR or methylation being a major factor in ME/CFS.
 

Gingergrrl

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According to Valentijn, there isn't much a statistical difference. I guess my poll is lacking allot of data without the "none" option.
Yeah, to be honest I really do not know or understand much about this area. I just got an e-mail from 23andMe that my raw data is in but have not had a chance to look at it yet. Maybe my CFS doctor meant that 95% of the patients he had seen had the compound heterogyzous on MTHFR like me. I really am not sure and don't want to quote him wrong!
 

drob31

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It's possible that there are MTHFR SNPs which aren't tested by 23andMe that are having an impact. It's also possible that other genes involved with folate or B12 are malfunctioning in different places for different ME patients.

But those are just possibilities - the data which I currently have access to simply doesn't support the possibility of MTHFR or methylation being a major factor in ME/CFS.

Interesting, well maybe this poll could add to your data in some way if enough people vote?

Looking at your chart, MAO looks suspect.
 

drob31

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Yeah, to be honest I really do not know or understand much about this area. I just got an e-mail from 23andMe that my raw data is in but have not had a chance to look at it yet. Maybe my CFS doctor meant that 95% of the patients he had seen had the compound heterogyzous on MTHFR like me. I really am not sure and don't want to quote him wrong!

You can run it through geneticgenie.com to get your detox/methylation profiles for free. I'm compound hetero as well. I keep seeing ALOT of people say they are compound hetero. Even Ben Lynch is compound hetero.


EDIT: Look at the poll results, compound hetero is already starting to take the lead.
 
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Valentijn

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Interesting, well maybe this poll could add to your data in some way if enough people vote?
Possibly, but unlikely. I wouldn't know where the overlap is between people I have data for and those who are voting. And I prefer to specify that I'm looking at results of ME patients - people who have or have had PEM.
Looking at your chart, MAO looks suspect.
How so? Yasko has the slow version as the "risk" factor, as it implies less tolerance for methyl groups when supplementing B12. But the slow version is also the common version. It's also important to remember that any involvement by VDR, MAOA, and COMT are peripheral to methylation at best - they don't effect how well you methylate, merely how well you supposedly tolerate methylB12.
 

Valentijn

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You can run it through geneticgenie.com to get your detox/methylation profiles for free. I'm compound hetero as well. I keep seeing ALOT of people say they are compound hetero. Even Ben Lynch is compound hetero.
If someone is heterozygous for both on 23andMe results, there's only a 50% chance that they are functionally compound heterozygous. If both mutations are on the same strand, then the other strand picks up the slack and it's just the same as if someone were only heterozygous for C677T - 65% functionality. But if both mutations are on opposite strands, then there is no normal strand to compensate for the mutations, and functionality is down to 30% just as it would be if homozygous for C677T.

If you have 23andMe results from one or both of your parents, you might be able to figure out if you're actually compound heterozygous, but otherwise it's just a 50/50 possibility. However a high-veggie diet or normal methylfolate supplementation has been shown to completely correct for both folate levels and associated disease risk in either case.
 
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MeSci

ME/CFS since 1995; activity level 6?
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If someone is heterozygous for both on 23andMe results, there's only a 50% that they are functionally compound heterozygous. If both mutations are on the same strand, then the other strand picks up the slack and it's just the same as if someone were only heterozygous for C677T - 65% functionality. But if both mutations are on opposite strands, then there is no normal strand to compensate for the mutations, and functionality is down to 30% just as it would be if homozygous for C677T.

If you have 23andMe results from one or both of your parents, you might be able to figure out if you're actually compound heterozygous, but otherwise it's just a 50/50 possibility. However a high-veggie diet or normal methylfolate supplementation has been shown to completely correct for both folate levels and associated disease risk in either case.
Ah - so most (all?) people replying 'compound heterozygous' and/or the person who replied 'compound homozygous' may not actually be, as they don't know? I had assumed that it just meant hetero/homo for both, and maybe others did too?

I'm very interested in what you say about veggies. I've been trying to find out what kind of folate you get from food and whether it makes any kind of difference in methylation, but couldn't find the info.

What form is the folate in in vegetables (and other folate-containing foods)? Does the methylation only occur in the body after consumption?