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

Lynn_M

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Sea, I believe Clairemont is asking if a male G/A for rs7255464 would suffer pathogenic consequences from having heterozygous alleles for G6PD. And similarly, what consequences would a female homozygous for A/A experience?

If a male was reported as having an A allele, or a female was reported as having A/A, they would have G6PD deficiency. See this.

Edited to remove incorrect information.
 
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Sea

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Sea, I believe Clairemont is asking if a male G/A for rs7255464 would suffer pathogenic consequences from having heterozygous alleles for G6PD. And similarly, what consequences would a female homozygous for A/A experience?

For the male, it would depend if the A rs7255464 allele was on the X or on the Y chromosome. Since G6PD is an X-linked recessive genetic condition, if the A was on the Y chromosome, there would be no impact. If the A of the male was on the X chromosome, or for the A/A female, they would have G6PD deficiency. See this.
This mutation is on the X chromosome. A male only has one X chromosome so there is no heterozygous for males on this one. He either has one fully functioning gene or one faulty gene.
 

Lynn_M

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Sea,
So on a 23andMe report on rs7255464, or any other x-linked gene, would 23andMe report just one allele for males? And if they do report two alleles, where does the second one come from, if there aren't any on the Y chromosome? Since Clairemont reports GG, does that make Clairemont a female?

After reading your last post, I want to edit my last post to remove the inaccuracies, but I don't want to commit any more errors.
 

Valentijn

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So on a 23andMe report on rs7255464, or any other x-linked gene, would 23andMe report just one allele for males?
Yes, SNPs on the X chromosome only show one allele on the 23andMe report for males. In the raw data it would like "G-" or "A-" or similar for a male. For a female it would show "GG", "AG", etc.

And if they do report two alleles, where does the second one come from, if there aren't any on the Y chromosome?
I'm not sure what you mean. Males will have a Y chromosome, but those genes are unrelated to the genes on the X chromosome. Males have one allele for every SNP on the X chromosome, period.

That's why they are especially vulnerable to inheriting recessive X-linked diseases from their mothers. The only have one allele, so a pathogenic allele which would be dominated by a healthy allele in a woman, would be all by itself in a man, and would basically act like being homozygous for the pathogenic allele.

Since Clairemont reports GG, does that make Clairemont a female?
Yes, if someone has two alleles for a SNP on the X chromosome, they are female. Or there's a mistake from 23andMe.
 
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mgk

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I recently did a blood test to verify the genetic report. To recap, my genetic report said I had the Mediterranean variant rs5030868 (hemizygous). Here's the blood test result:



5 is the result, 146-376 is the reference range.
 
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btdt

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I found this news release today thought I would share it here
https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm551185.htm

I have not been to 23 and me since reading it so don't know how it has affected the site or if it has.

I have yet another infected tooth have had trouble with lidocaine and other caines in the past and went searching for a genetic reason and possible substitute for caines for up coming extraction. I had two infected teeth removed last month and had what I thought was a seizure at the time.. caine reactions are not new to me some have been long lasting. I brought his up again yesterday and now am searching a reason for these caine reactions... and a possible substituted drug to use during the extraction.. a safe drug.

I was here
To make sure lidocaine and prilocaine topical is safe for you, tell your doctor if you have:

  • a blood cell disorder called methemoglobinemia;
  • liver disease;
  • a genetic enzyme deficiency called glucose-6-phosphate dehydrogenase (G6PD) deficiency; or
  • a family history of methemoglobinemia, or any genetic enzyme deficiency.
While searching for G6PD this page came up so here I am again... new FDA rules apparently allows 23 and me talk about some problems and not others..first link above

Is this my problem with caine drugs.. I surely have not clue as of yet and am still infected and on antibiotics.. yet again My extraction apt has been pushed back to try to sort out what sort of drug I can use... so I am trying to speed this along by finding out. May just not be up to it yet.

Do any other ME people have a problem with caine drugs if you what is an alternative drug for dental surgery?

At this point I don't care if it costs more just don't care I want this tooth out without a reaction if possible.

I have searched here for lidocaine and dental freezing and came up empty so this may be just my problem.
 
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Ron Davis has just brought up red blood cell deformability as a possible issue in some patients with me/cfs. I was looking at research on deformability and there is a link to G6PD, so I thought it was worth resurfacing this old thread.

The paper below (Tang, 2015) shows that linkage, and also ties it into a lot of other familiar metabolic components, like NADPH, AMPK, glutathione, etc. I'm not educated enough in cellular biology to figure out how relevant this is, but I hope by posting it here someone with the relevant skills who had not seen this before can help us all understand things a little better!


https://www.ncbi.nlm.nih.gov/pubmed/25556665

Inability to maintain GSH pool in G6PD-deficient red cells causes futile AMPK activation and irreversible metabolic disturbance.
Tang HY1, Ho HY, Wu PR, Chen SH, Kuypers FA, Cheng ML, Chiu DT.
Author information
Abstract

AIMS:
Glucose 6-phosphate dehydrogenase (G6PD) is essential for maintenance of nicotinamide dinucleotide hydrogen phosphate (NADPH) levels and redox homeostasis. A number of drugs, such as antimalarial drugs, act to induce reactive oxygen species and hemolytic crisis in G6PD-deficient patients. We used diamide (DIA) to mimic drug-induced oxidative stress and studied how these drugs affect cellular metabolism using a metabolomic approach.

RESULTS:
There are a few differences in metabolome between red blood cells (RBCs) from normal and G6PD-deficient individuals. DIA causes modest changes in normal RBC metabolism. In contrast, there are significant changes in various biochemical pathways, namely glutathione (GSH) metabolism, purine metabolism, and glycolysis, in G6PD-deficient cells. GSH depletion is concomitant with a shift in energy metabolism. Adenosine monophosphate (AMP) and adenosine diphosphate (ADP) accumulation activates AMP protein kinase (AMPK) and increases entry of glucose into glycolysis. However, inhibition of pyruvate kinase (PK) reduces the efficacy of energy production. Metabolic changes and protein oxidation occurs to a greater extent in G6PD-deficient RBCs than in normal cells, leading to severe irreversible loss of deformability of the former.

INNOVATION AND CONCLUSION:
Normal and G6PD-deficient RBCs differ in their responses to oxidants. Normal cells have adequate NADPH regeneration for maintenance of GSH pool. In contrast, G6PD-deficient cells are unable to regenerate enough NADPH under a stressful situation, and switch to biosynthetic pathway for GSH supply. Rapid GSH exhaustion causes energy crisis and futile AMPK activation. Our findings suggest that drug-induced oxidative stress differentially affects metabolism and metabolite signaling in normal and G6PD-deficient cells. It also provides an insight into the pathophysiology of acute hemolytic anemia in G6PD-deficient patients.