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

[Lynn_M]

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.

 

[Sea]

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]

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]

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.

 

[mgk]

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.

 

[btdt]

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.

 

[btdt]

on this list
http://www.eupedia.com/genetics/genetic_diseases.shtml
Description Chromosome Gene SNP Risk alleles
G6PD Deficiency X G6PD rs1050828 CC, CT, TT A, C

They give only one snp to check... same as for other disorders.

 

[Murph]

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.

 

[Gondwanaland]

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.

I find this info very confusing, because it must be surely underestimated!

 

[Gondwanaland]

https://www.sciencedirect.com/science/article/pii/S0163725820303193

Pharmacology & Therapeutics
Volume 222, June 2021, 107788

Current investigations on clinical pharmacology and therapeutics of Glucose-6-phosphate dehydrogenase deficiency

 

[Gondwanaland]

G6PDD

Glucose-6-phosphate dehydrogenase deficiency (several studies published about polymorfisms from Mediterranean, African and SE Asian continents)
≠
Glucose-6-phosphate dehydrogenase allele deletion (I am having a hard time in finding studies on this)

My husband carries a G6PD allele deletion and is 99.9% of northern European descent, also has downstream deleterious SNPs, but neither he or his siblings ever had anemia or jaundice, so any health complication they might have will never be associated with G6PDD.

My husband was a sports enthusiast in his teens and early 20's, but after some infections he dropped sports and since 2004 suffers from extreme PEM.

https://www.sciencedirect.com/science/article/pii/S0006497120617190
Volume 136, Issue 11, 10 September 2020, Pages 1225-1240
Journal home page for Blood

Inherited Anemias
Glucose-6-phosphate dehydrogenase deficiency
Authors from Tanzania and Italy

Abstract
Glucose 6-phosphate dehydrogenase (G6PD) deficiency is 1 of the commonest human enzymopathies, caused by inherited mutations of the X-linked gene G6PD. G6PD deficiency makes red cells highly vulnerable to oxidative damage, and therefore susceptible to hemolysis. Over 200 G6PD mutations are known: approximately one-half are polymorphic and therefore common in various populations. Some 500 million persons with any of these mutations are mostly asymptomatic throughout their lifetime; however, any of them may develop acute and sometimes very severe hemolytic anemia when triggered by ingestion of fava beans, by any of a number of drugs (for example, primaquine, rasburicase), or, more rarely, by infection. Approximately one-half of the G6PD mutations are instead sporadic: rare patients with these mutations present with chronic nonspherocytic hemolytic anemia. Almost all G6PD mutations are missense mutations, causing amino acid replacements that entail deficiency of G6PD enzyme activity: they compromise the stability of the protein, the catalytic activity is decreased, or a combination of both mechanisms occurs. Thus, genotype-phenotype correlations have been reasonably well clarified in many cases. G6PD deficiency correlates remarkably, in its geographic distribution, with past/present malaria endemicity: indeed, it is a unique example of an X-linked human polymorphism balanced through protection of heterozygotes from malaria mortality. Acute hemolytic anemia can be managed effectively provided it is promptly diagnosed. Reliable diagnostic procedures are available, with point-of-care tests becoming increasingly important where primaquine and its recently introduced analog tafenoquine are required for the elimination of malaria.

(C) Time course of Hb levels in a large cohort of children with P falciparum malaria who received antimalarial treatment with a drug combination (Lapdap) containing dapsone. Eleven percent of G6PD-deficient hemizygous boys and 0.5% of heterozygous girls required blood transfusion. All of these children were in clinical trials under appropriate medical supervision; there were no deaths (there might have been outside of clinical trials).


AHA = acute hemolytic anemia

 

[Gondwanaland]

Wait wait wait, just now I understand
It is an X-linked gene
So obviously men only carry one allele
So I must look into this one allele!
🤦‍♀️😬😅

 

[Gondwanaland]

23andme lists 7 rs SNPs for us

He carries one with decreased function and I carry another one

 

[Gondwanaland]

Here is a 2023 state-of-the-art publication about this:
(the supplemental file is a spreadsheet with all variations analyzed so far)

https://www.sciencedirect.com/science/article/pii/S0002929723000034

Volume 110, Issue 2, 2 February 2023, Pages 228-239
Journal home page for The American Journal of Human Genetics

Functional interpretation, cataloging, and analysis of 1,341 glucose-6-phosphate dehydrogenase variants

Interpreting the effect of sequence variation in G6PD can be used to predict which individuals are at risk for adverse drug reactions. By analyzing data from publications and databases, we provided interpretations for 186 G6PD variants of uncertain significance, bringing the total number of interpreted variants to 400.

 

[Gondwanaland]

Here is something very interesting:

https://www.mdpi.com/2227-9067/10/7/1172

Children 2023, 10(7), 1172

The Genetics of Glucose-6-Phosphate-Dehydrogenase (G6PD) and Uridine Diphosphate Glucuronosyl Transferase 1A1 (UGT1A1) Promoter Gene Polymorphism in Relation to Quantitative Biochemical G6PD Activity Measurement and Neonatal Hyperbilirubinemia

However, quantitative screening tests for G6PD enzyme activity proved unsatisfactory in estimating the risk for significant neonatal hyperbilirubinemia, especially in heterozygous females that could present phenotype overlap between normal homozygotes, heterozygotes, and deficient homozygotes, resulting in a continuum of intermediate G6PD activity.

 

[xploit316]

This is very interesting. Some good information of things to avoid for people with G6PD defiency. A couple of things to also avoid which is not mentioned in this article are high dose Vitamin C and bitter gourd.

https://www.healthline.com/nutritio...d-supplements-to-choose-and-avoid#what-to-eat