Anybody with ME/CFS also positive for glucose-6-phosphate dehydrogenase deficiency?

[richvank]

Hi, all.

I'm just wondering if anyone here who has ME/CFS has also been found to be positive for glucose-6-phosphate dehydrogenase deficiency (G6PDD).

This is starting to be of some interest in autism, particularly in people of Middle Eastern or African descent, in which
there is a greater prevalence of G6PDD, probably because malaria selected for people who had this genetic variation
in the past.

This is the most common genetic mutation in the human population. It causes red blood cells to be less able to
recycle their glutathione, and can thus lead to early death of these cells. This is normally a disadvantage, but the benefit in malaria is that the malaria
parasites inhabit the red blood cells and depend on the antioxidant system in the red blood cells for their survival. GDPDD would hamper control of oxidative stress,
and that could help to kill the red cells in which the malaria parasites reside, and hence to knock out the parasites as well.

Given that I believe that both ME/CFS and autism begin in most cases with depletion of the chemically reduced form
of glutathione, and that red blood cells are normally net producers and exporters of glutathione, it would make
sense from a theoretical point of view that having G6PDD would tend to increase the susceptibility to developing
ME/CFS or autism.

I don't see anything about this in the ME/CFS research literature, and am wondering if this connection really shows up in the ME/CFS population.

Thanks.

Rich

 

[searcher]

For those of us with 23andme, you can see whether you have one of the two common mutations that cause G6PDD deficiency under "carrier status." It says that 400 million people have this deficiency. I also noticed the gene is carried on the X chromosome, so should be more common in males (which would fit autism but not ME/CFS.)
I don't have the deficiency according to 23andme, but the two SNPs they report on are generally only found in people with recent African ancestry, which I don't have.

 

[mgk]

I know Rich is no longer with us, but I came across this post and thought it was worth resurfacing. I recently learned that I'm G6PD deficient and have been learning more and more about it.

There are a lot of genetic variations, so it's not sufficient to look at a few SNPs and conclude that you don't have it. A functional test is really the best way to find out. Having said that, there are a few SNPs that can be looked at. ClinVar has 31 labeled as "pathogenic," and there's probably more. Of the 31 pathogenic SNPs, I found that 4 of them were currently available in 23andMe. They're listed below, along with the risk alleles:

rs1050828 C or T, risk allele T
rs1050829 C or T, risk allele C
rs5030868 A or G, risk allele A
rs72554664 C or T, risk allele T
​

I also found this great summary of research on specific nutrients that are relevant to G6PD deficiency:

 

[roxie60]

Do you have a link to the G6PD deficiency list? Thanks for sharing.

 

[mgk]

Do you have a link to the G6PD deficiency list? Thanks for sharing.

It's from a book called Myopia Manual, published in 2004, ISBN 158961271X. Here's a link to the particular page on Google Books: https://books.google.com/books?id=BX2r1F-GQREC&pg=PA157

 

[Sea]

I know Rich is no longer with us, but I came across this post and thought it was worth resurfacing. I recently learned that I'm G6PD deficient and have been learning more and more about it.

There are a lot of genetic variations, so it's not sufficient to look at a few SNPs and conclude that you don't have it. A functional test is really the best way to find out. Having said that, there are a few SNPs that can be looked at. ClinVar has 31 labeled as "pathogenic," and there's probably more. Of the 31 pathogenic SNPs, I found that 4 of them were currently available in 23andMe. They're listed below, along with the risk alleles:

rs1050828 C or T, risk allele T
rs1050829 C or T, risk allele C
rs5030868 A or G, risk allele A
rs72554664 C or T, risk allele T
​

I also found this great summary of research on specific nutrients that are relevant to G6PD deficiency:

View attachment 11327

mgk with regard to 23andme having 4 of the pathogenic snps, have you looked at all the i numbers as well as the rs numbers? My 23andme result for the G6PD gene has 59 snps, 37 of them are i numbers which need more digging to find their corresponding rs numbers

 

[mgk]

mgk with regard to 23andme having 4 of the pathogenic snps, have you looked at all the i numbers as well as the rs numbers? My 23andme result for the G6PD gene has 59 snps, 37 of them are i numbers which need more digging to find their corresponding rs numbers

No, I only matched the ones that had an associated rs number in 23andme. It didn't occur to me to look at the i numbers (oops). It should be possible to cross-reference based on the chromosome position and the allele options listed in 23andme though. I just took a quick glance and it's looking like quite a few of those i numbers are pathogenic. Thanks for bringing this up, I'll post an updated list soon.

 

[mgk]

Here's a more comprehensive list of SNPs.

Since there are so many of them, I think the fastest way to check them all is to go to this page in your 23andme account: https://www.23andme.com/you/explorer/gene/?gene_name=G6PD

Open it in a new browser window alongside this one, then use the browser's search function to check each one.

• rs72554664: C or T, risk allele T
• i5012739 (rs72554665): A or C, risk allele A
• i6010622 (rs398123546): A or G, risk allele A
• i6010588 (rs137852317): C or T, risk allele T
• i5008448 (rs137852336): C or T, risk allele T
• i6010592 (rs137852335): C or G, risk allele G
• i6010580 (rs137852316): C or T, risk allele T
• i6010621 (rs137852334): A or G, risk allele A
• i6010512 (rs137852329): G or T, risk allele T
• i5008459 (rs137852345): A or G, risk allele A
• i6010628 (rs34193178): C or G, risk allele G
• i3003411 (rs5030869): C or T, risk allele T
• i5008436 (rs137852327): C or T, risk allele T
• i6010663 (rs137852346): C or T, risk allele T
• i5008440 (rs137852330): A or G, risk allele A
• rs5030868: A or G, risk allele A
• i5008442 (rs267606836): A or G, risk allele A
• i3003413 (rs5030872): A or T, risk allele A
• i6010596 (rs78365220): A or G, risk allele G
• rs1050829: C or T, risk allele C
• i5008441 (rs267606835): C or G, risk allele C
• rs1050828: C or T, risk allele T

For those that don't know, i numbers are ids internal to 23andme, whereas rs numbers are used in the wider scientific community. I inferred the rs numbers in parentheses based on the chromosome position and allele versions listed in 23andme.

Note that the severity varies from SNP to SNP. If you have one of them, the best thing to do is to inform your doctor and get an actual blood test for G6PD deficiency. It can also be informative to do a Google search for the rs number and look at the studies associated with it. Sometimes Google doesn't come up with anything for the rarer SNPs. In that case, you can usually get more information about it by entering it into ClinVar.

 

[out2lunch]

i3003413 (rs5030872): A or T, risk allele T
i5008441 (rs267606835): C or G, risk allele G

Thanks, mgk, for the info!

These are the only two I had SNPs for, both homozygous.

My question is, how did you determine the rs number for these SNPs and the subsequent risk alleles? Obviously it wasn't through 23andMe. But which sites give the correlating data?

 

[Amaya2014]

I know Rich is no longer with us, but I came across this post and thought it was worth resurfacing. I recently learned that I'm G6PD deficient and have been learning more and more about it.

I am G6PD deficient. Hemolytic anemia was something I considered initially, but, the symptoms didn't match. Do you think G6PD adds to CFS/SEID in anyway?

 

[aquariusgirl]

would Prometheus or livewello pick this up?

 

[mgk]

My question is, how did you determine the rs number for these SNPs and the subsequent risk alleles? Obviously it wasn't through 23andMe. But which sites give the correlating data?

You have to dig for it a little bit, but it comes from ClinVar. I'll use one of the SNPs you mentioned as an example. For i3003413, if you look in 23andMe, you'll see that it says the chromosome position is 153762655.

Keeping that in mind, go to the ClinVar search page. On the first line, select "Gene Name" from the dropdown list, then enter "G6PD" in the text area. On the second line, select "Base Position for Assembly GRCh37" and then enter "153762655."

Slight technical aside: Why did we pick assembly GRCh37? Because that's what 23andMe uses, based on this FAQ entry.

When you do the search, you should get two results. This is why the chromosome position isn't enough. You need to compare the allele options to ensure it's the same SNP. Open the two results, and look where it says HGVs. (Make sure to expand the list by clicking on "more.")

An HGV is a more technical way to describe variations. I'm not an expert in this stuff but I know roughly how to read some of them. Anyway, you're looking for the HGV that starts with "NC_000023.10:g", which essentially means it's describing the variation by the chromosome position. Again, you want the one that says "GRCh37."

For the first result, you'll see "NC_000023.10:g.153762655T>A", which is saying "the variation at chromosome position 153762655 where the T was switched to an A." Looking at 23andMe, the allele options for i3003413 are A or T, so this is the SNP we're looking for, and we can conclude that the risk allele is A. The rs number is on the same page: rs5030872.

While I was explaining this, I realized that I made a mistake with this SNP. The actual risk allele is A. So I went back and double-checked all of them and updated the list. There were 2 mistakes, and it turns out that the mistakes were in the ones you mentioned. Good news: you don't have those mutations. Sorry about that, I hope I didn't cause you any anguish.

 

[out2lunch]

While I was explaining this, I realized that I made a mistake with this SNP. The actual risk allele is A. So I went back and double-checked all of them and updated the list. There were 2 mistakes, and it turns out that the mistakes were in the ones you mentioned. Good news: you don't have those mutations. Sorry about that, I hope I didn't cause you any anguish.

I'm LOLing because your mistake was actually helpful!

I've been bugging my doc to order G6PD testing on me because of elevated arabinose, and he was reluctant to do it until I mentioned my homozygous SNPs!

BTW… did Rich or anyone else make any kind of connection between the G6PD deficiencies seen in ME/CFS and subsequent lack of the SNPs? Maybe I'm misunderstanding the info, but I'm under the impression that most of us do not have these SNPs for G6PD. Is that correct?

While it's possible I won't be G6PD deficient, I won't be surprised if I am, given how much ribose helps.

 

[mgk]

I am G6PD deficient. Hemolytic anemia was something I considered initially, but, the symptoms didn't match. Do you think G6PD adds to CFS/SEID in anyway?

Hemolytic anemia is only the acute worst-case scenario for people with G6PDD. There's still a chronic glutathione deficiency and all of the problems that come with that. If glutathione deficiency is implicated in CFS -- and I think that it is -- then I believe G6PDD does play a role in CFS.

 

[mgk]

would Prometheus or livewello pick this up?

I don't know about Livewello, but Promethease would. That's actually how I found out I had it.

 

[mgk]

I'm LOLing because your mistake was actually helpful!

I've been bugging my doc to order G6PD testing on me because of elevated arabinose, and he was reluctant to do it until I mentioned my homozygous SNPs!

Hah, I'm glad it worked out, but I still feel bad for posting bad information. I'll try to be more careful next time.

What's the connection between G6PD and arabinose? I haven't heard that before.

BTW… did Rich or anyone else make any kind of connection between the G6PD deficiencies seen in ME/CFS and subsequent lack of the SNPs? Maybe I'm misunderstanding the info, but I'm under the impression that most of us do not have these SNPs for G6PD. Is that correct?

I don't think there's any connection. The problem is that there are a lot of variations. Even the long list I gave above is a partial list because 23andMe has yet to sequence some SNPs that are listed in ClinVar. In other words, checking SNPs is a good way to see if you have it, but not a good way to see if you don't.

For the record, I have the rs5030868 variation.

While it's possible I won't be G6PD deficient, I won't be surprised if I am, given how much ribose helps.

Please post an update when you find out. I haven't tried d-ribose myself, but like you said, it makes sense that it would help.

 

[out2lunch]

What's the connection between G6PD and arabinose? I haven't heard that before.

Dr Weyrich has claimed that elevations in arabinose on the OAT urine test can be caused by problems in the pentose phosphate pathway. Arabinosuria has been previously linked to G6PD deficiency, so having elevated arabinose on OAT results could be an indication of a G6PD deficiency.

 

[Amaya2014]

Hemolytic anemia is only the acute worst-case scenario for people with G6PDD. There's still a chronic glutathione deficiency and all of the problems that come with that. If glutathione deficiency is implicated in CFS -- and I think that it is -- then I believe G6PDD does play a role in CFS.

I looked up the glutathione deficiency...very interesting. Are you doing anything to increase glutathione? If so, is this having a significant effect on your CFS/SEID?

 

[mgk]

I looked up the glutathione deficiency...very interesting. Are you doing anything to increase glutathione? If so, is this having a significant effect on your CFS/SEID?

I've tried many things but none of them have helped as much as I'd hoped. Things usually seem promising for a while and then they stop working for some reason. I'm still actively trying things though and I'll definitely post an update here if I ever find anything that makes a significant difference in the long term.

 

[Sea]

@mgk my list is very different to yours. Which version of the 23andme chip were you tested on? Mine was the version 3 chip