Preprint Spironolactone for ME/CFS in a Patient Homozygous for rs5522 (I180V): A Case Report, 2026, Donnellan et al
- Thread starter forestglip
- Start date
DonnellanP
Established Member
Well, I think it was MY reasoning because I am the one who helped reason it and my name is on the mechanism paper with my coauthors that shows increased binding affinity.
Wishing you all the best in your health journey!
~Patricia Donnellan, MPH
https://authors.elsevier.com/c/1mt6x,99wrFyt
Venicequeenf
Established Member (Voting Rights)
This is from MyHeritage raw data
So I think there is the discrepancy now between TT being Ile Ile and TT being Val Val?
So I think there is the discrepancy now between TT being Ile Ile and TT being Val Val?
Last edited:
Utsikt
Senior Member (Voting Rights)
Something isn’t proven just because it’s written in a paper.
I again ask that you provide the reason you think that T reported by 23andME or any other company would mean translation into valine, because this doesn't seem to make sense. There is no thymine (T) molecule at this location in the DNA on either strand if valine is included in the protein.
Also, we already know that the frequency of this mutation in ME/CFS is very similar to that of healthy people because DecodeME tested it with over 15 thousand cases. I copied DecodeME's result for this variant into an earlier post.
Note the A1FREQ_CASES value of 0.87 (frequency of T allele), which translates to about 75% of cases (0.87^2) being homozygous for the T allele and only 1.7% of cases ((1-0.87)^2) being homozygous for the C allele.
This means that the majority of people who check their genome, whether healthy or unhealthy, will find TT here (or AA if the company uses a different reference strand).
OK, but is the horse taking Spironolactone?—seems like that is the important question.
jnmaciuch
Senior Member (Voting Rights)
this paper that you are a coauthor on actually does not say that at all. It only shows increased transcriptional activation downstream of ligand binding to the MR. It does not provide any evidence that this is due to increased binding affinity between the ligand and the receptor’s binding site that would lead to cortisol being “stolen” from the GR. That paper’s own discussion acknowledges that the exact mechanism of increased transcriptional activation is unclear and provides a few speculations, none of which have to do with the theory you’re claiming here. Do you have any expertise in molecular biology or other published research to support these claims?
Last edited:
jnmaciuch
Senior Member (Voting Rights)
The highlighted part is the refseq number, which is really just supposed to identify the location of the SNP rather than the actual genotype. So if you wanted to talk about a specific genotype you’d say rs5522TT, or rs5522(I180V) if it ends up being a non-synonymous mutation, or something like rs5522C>T in the case of a GWAS (since C is the reference allele despite being the more rare one). What you’re showing just says “At the location of known variable region identified by rs5522, you have the TT genotype.”
Unfortunately it can get confusing because sometimes authors will use the refseq number on its own as a short hand to refer to the rare/disease-associated mutation, leading to sentences like in the linked mechanism paper where they talk about “rs5522 vs. wild-type” assuming that people will understand they mean the specific C allele variant at rs5522. I think that may be partly where all the confusion stems from