SERPINA1 and A1-Antitrypsin Deficiency

[mariovitali]

I wanted to point your attention to Antitrypsin Deficiency.

Many of you have sent me their DNA Data so i have a number of DNA files of ME/CFS individuals but also from individuals having other syndromes including Post-Finasteride Syndrome, Post-Accutane Syndrome and others.

As already discussed i sent an email to @Janet Dafoe (Rose49) with a 32-page document outlining the elements of the Hypothesis as to what is behind ME/CFS.

I would also like to disclose that the same 32-page document was forwarded to :

a) Professor Maureen Hanson (Cornell University)
b) Professor Derya Unutmaz (Jackson Labs)
c) Professor Richard Deth (Northeastern University)

...hoping that they will find useful information that could help them progress their Research.

Their first comments are very supportive so let's keep our fingers crossed.


From this document we read :

I would kindly ask you to look for SNPs in the following Pathogenic Genes :


rs17580 - Risk 'A'
rs61761869 - Risk 'A'


I will forward these Genes to them so they may evaluate to their Cohorts.

In my Cohort of 64 people, around 10% were found to have rs17580 risk allele and 1 was found to have the rs61761869 Allele

 

[Runner5]

Parasites are listed under bacteria....that's just...bothering my OCD so oooo ooo much

 

[mariovitali]

Parasites are listed under bacteria....that's just...bothering my OCD so oooo ooo much

Well spotted, Thank you

 

[drob31]

Well spotted, Thank you

Could change it to "pathogens" and still be correct.

 

[Gondwanaland]

rs17580 - Risk 'A'

'A' allele is good for this SNP

 

[mariovitali]

@Gondwanaland : According to dbsnp, A is the Minor Allele Frequency with 0.01 and it is Pathogenic.

You can also search in PR for Antitrypsin Deficiency, it has been mentioned quite some times.

@All

it should becoming more clear that there are so many "Liver Stressors" that could potentially set the stage for ME/CFS. Unfortunately in the "Gallbladder and Bile Acid Circulation " section of the 32-page document i forgot to add Holecystectomy : (Removal of Gallbladder)

Patients with cholecystectomy had more comorbidities (5.2±3.3 vs 3.3±2.5; P <0.001), particularly chronic fatigue syndrome, fibromyalgia, major depression, and severe anxiety. Fifty-nine percent of those with a cholecystectomy had been hospitalized in the past year (vs 45%; P <0.001) (Table 2). Prior cholecystectomy patients had poorer quality of life based on the PAGI-QOL (2.2±1.1 vs 2.6±1.1; P=0.004) and the SF-36 health survey (physical: 32±10 vs 34±10; P=0.05; mental: 36±13 vs 38±12; P=0.13). Table 3depicts the Rome III categorization of the patients. There were no significant differences between the cholecystectomy groups for any of the Rome III categories.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3891205/

Although i cannot be certain on the ultimate result, this is why i see the Theory of "Metabolic Trap" as overly simplistic for the problem at hand. Of course it may help some patients.

 

[Ema]

rs17580

TT

rs61761869

GG

 

[mariovitali]

@Ema @Gondwanaland

Thank you for providing your results. I am trying to explain as much as i can the different faces that "Liver Stressors" can take. For some it may be Hemochromatosis, for others Gilbert's for others NAFLD...even Rocky Mountain Fever.

So according to this Theory each ME/CFS patient should look for any of the number of Liver Stressors being listed on the Google sheet i sent.

Problems can hide notoriously well. For example i was talking to a girl, waiting for the "a-ha" moment where a Liver stressor is identified. It didn't happen so nothing Liver-related was found.

Then she came back to me the next day, saying that she asked her mother to tell her for any incidences and sure enough she had an incidence of white stools (= probably means cholestasis) when she was a very young .

 

[mariovitali]

Has anyone else managed to see these SNPs?

rs17580 - Risk 'A'
rs61761869 - Risk 'A'

 

[Dan_USAAZ]

Has anyone else managed to see these SNPs?

rs17580 - Risk 'A'
rs61761869 - Risk 'A'

I am rs17580(A;A). This SNP is a little confusing, as per what @Gondwanaland posted, Prometheus lists this genotype as the common, low/no risk variant.

Also, SNPedia states the following in regard to this SNP:

"Due to orientation, be careful when interpreting results for this SNP which is an ambiguous flip."

SNPedia describes the ambigious flip as follows.

"While at this early stage *all data is suspect*, some data is even more so. Genotypes which cannot easily be distinguished from their flipped form are very prone to confusion, including by scientists when they publish their results [PMID 18154681].

Since DNA is composed of 2 antiparallel strands, there is ambiguity over which strand to look at. dbSNP uses the assembled chromosome to establish a plus and a minus strand. Sometimes other sources rely on the orientation of an individual read, the encoded gene, or other information. Nearly every snp in SNPedia has an Orientation field on the righthand side infobox which shows as 'plus' or 'minus'.

Elsewhere you may see the terms orientation and strand used interchangably.

If a microarray claims that you are an rs1234(A;A) for a SNP in which the other allele is G, but dbSNP claims that this is a C;T SNP, then logically we flip your results over and call you a rs1234(T;T). This is safe and reasonable.

Unfortunately if this was instead a SNP where the two alleles are A or T the same flipping logic falls down. We don't (yet) have a way to know for sure if you should be flipped or not, since both forms of your flip rs1234(A;A) and rs1234(T;T) are possible. That problem occurs for the homozygous forms of A/T and C/G SNPs, and remains hard, with several possible avenues of attack, but no clear solution.

Be extra skeptical of these cases[edit]

• an (A;A) genotype call when the alleles are A and T
• a (T;T) genotype call when the alleles are A and T
• a (C;C) genotype call when the alleles are C and G
• a (G;G) genotype call when the alleles are C and G"

This issue appears to relate to this SNP, but my limited knowledge of genetics does not allow me to fully understand how to interpret correctly.

 

[mariovitali]

My current understanding is that the alleles described are the pathogenic ones. As an example :

https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=17580

In any case, if you are homozygous to any of these ones it wouldn't hurt to get tested for A1-Antitrypsin Deficiency.