Unfolded Protein Response and A Possible Treatment for CFS

[skwag]

Hi @jump44,

In the case of primary biliary cirrhosis, which is an autoimmune condition, treatment does include UDCA as discussed in the Wikipedia entry, but it is controversial.

Most of the patients (>90%) have anti-mitochondrial antibodies (AMAs) against pyruvate dehydrogenase complex (PDC-E2), an enzyme complex that is found in the mitochondria.

An AMA test can be used to help diagnose.

 

[mariovitali]

@jump44 @Gondwanaland

These are the results for Gilbert's :

We see that enterohepatic circulation,liver disease, nqo1 and -interestingly- Taurine is associated wtih Gilbert's (Please Note : These are just hypotheses).

After some reading, it appears that your husband should boost Phase II by :

1) Avoiding low-protein diets
2) Avoiding NSAIDs

Eat/take :

Cruciferous Vegetables, Eggs, Leeks, Limonene (or D-Limonene as a supplement), Milk Thistle,Onions, Raw Garlic.


Nutrients :

ALA, Folic Acid, Magnesium, Manganese, Methionine, NAC, Selenium, Taurine,B2,B5,B12,C, Zinc

 

[mariovitali]

Just wanted to make something clear regarding this message i sent : (FYI : @skwag)

I still have no answer from many people telling me that "they gave to the regimen a good try" and evaluate and disclose how they feel from following it.

What i tried saying is that there are not many people that have *actually* tried this regimen in its entirety (=a good try) and as a consequence i have no feedback.

So we have to see what happens when more people try the regimen.

 

[skwag]

What i tried saying is that there are not many people that have *actually* tried this regimen in its entirety (=a good try) and as a consequence i have no feedback.

It's good you corrected it, because I understood it the other way.

I think part of the problem may be that the regimen is complicated and and it becomes overwhelming for people, especially if they have any brain fog. One way to overcome this problem is to simplify the regimen, by taking a "cover all your basics" approach, as Freddd has done with his protocol. So instead of having people try to figure out what specific B-vitamins they need, just have them take a low dose B-complex. I think one of your recent posts was heading in this direction. Ahmo suggested a good B-complex.

As for minerals, I use this one, which covers the trace minerals.

My 2 cents.

 

[mariovitali]

@skwag

Yes, i absolutely agree on this.

To recap My current Regimen is as follows :


B1, B2 (as FMN) B3, B5, B6 (as P5P), B7, B9 (as Metafolin), B12 (as Dibencozide), K2, C
Choline (as Alpha GPC)
TUDCA 2 * 250 mg
Taurine

Minerals : Zinc, Selenium, Magnesium, Manganese, Molybdenum (all at roughly 50% RDA)

 

[mariovitali]

Topic matchings for UGTs :

car = constitutive androstane receptor
pxr = pregnane x receptor

*********Topic : ugt1a1 ***************
ugt1a1.csv : 87.84 %
ugt1a9.csv : 54.56 %
udpgluc.csv : 19.04 %
gilberts.csv : 17.54 %
glucuronidation.csv : 13.59 %
car.csv : 5.10 %
pxr.csv : 3.94 %
cyp3a4.csv : 1.55 %
bilirubin.csv : 1.54 %
cyp1a2.csv : 1.29 %
cyp1b1.csv : 1.28 %
cyp2d6.csv : 1.08 %
nqo1.csv : 0.99 %
sulforaphane.csv : 0.94 %
sulfotransferase.csv : 0.82 %
cyp1a1.csv : 0.70 %
nrf2.csv : 0.63 %
detoxification.csv : 0.50 %
esr1.csv : 0.46 %
sulfation.csv : 0.41 %
fmo3.csv : 0.40 %
p450.csv : 0.40 %
conjugation.csv : 0.40 %
cyp2e1.csv : 0.37 %
p450oxidoreductase.csv : 0.32 %
enterohepatic_circulation.csv : 0.32 %
mthfr.csv : 0.30 %
are.csv : 0.29 %
resveratrol.csv : 0.24 %
udpglcnac.csv : 0.19 %
hydrolysis.csv : 0.19 %
hepatocytes.csv : 0.19 %
cyp27a1.csv : 0.18 %
rxr.csv : 0.18 %
n-acetyltransferase.csv : 0.17 %
glutathione_stransferase.csv : 0.15 %
hepatotoxicity.csv : 0.15 %
pregnenolone.csv : 0.13 %
curcumin.csv : 0.13 %
triiodothyronine_levels.csv : 0.13 %
oxidation.csv : 0.10 %
tocotrienol.csv : 0.10 %
freet3.csv : 0.10 %
protease_inhibitor.csv : 0.09 %
ggt.csv : 0.09 %
liver_injury.csv : 0.08 %
finasteride.csv : 0.08 %
bile_acid.csv : 0.08 %
sod2.csv : 0.06 %
thioredoxin.csv : 0.05 %
rar.csv : 0.05 %
caloric_restriction.csv : 0.05 %
histone_deacetylase.csv : 0.05 %
sod1.csv : 0.05 %
cholestasis.csv : 0.04 %
steatohepatitis.csv : 0.04 %
acetylation.csv : 0.04 %
vitamin_k.csv : 0.04 %
nadph.csv : 0.04 %
nad.csv : 0.04 %
microbiome_humans.csv : 0.04 %
dht.csv : 0.03 %
liver_disease.csv : 0.03 %
oxidative_stress_protection.csv : 0.03 %
ginkgo.csv : 0.03 %
peroxiredoxin.csv : 0.03 %
isotretinoin.csv : 0.03 %
cox-2.csv : 0.03 %
nafld.csv : 0.03 %
serotonin_levels.csv : 0.03 %
neuroinflammation.csv : 0.02 %
n-acetylglucosamine.csv : 0.02 %
liver_regeneration.csv : 0.02 %
hmgcoa.csv : 0.02 %
glycoproteins.csv : 0.02 %
ros.csv : 0.02 %
er_stress.csv : 0.02 %
gut.csv : 0.02 %
cofactor.csv : 0.02 %
tau.csv : 0.02 %
mcp-1.csv : 0.02 %
probiotics.csv : 0.02 %
hydroxysteroid_dehydrogenase.csv : 0.02 %
fluoroquinolone.csv : 0.02 %
flavoprotein.csv : 0.01 %
glutamine.csv : 0.01 %
testosterone_production.csv : 0.01 %
mitochondrial_dysfunction.csv : 0.01 %
hgh.csv : 0.01 %
nac.csv : 0.01 %
biliary_cirrhosis.csv : 0.01 %
disulfide_bonds.csv : 0.01 %
adrenergic_receptor.csv : 0.01 %
p53.csv : 0.01 %
microglia.csv : 0.01 %
omega3.csv : 0.01 %
phosphorylation.csv : 0.01 %
caspase_human.csv : 0.01 %
inflammatory_response.csv : 0.01 %
vitamin_d3.csv : 0.01 %
reduced_glutathione.csv : 0.01 %
cortisol_levels.csv : 0.01 %
dhea.csv : 0.01 %
oxidative_stress_markers.csv : 0.01 %
crohns_disease.csv : 0.01 %
glycosylation.csv : 0.01 %
catalase.csv : 0.01 %
taurine.csv : 0.01 %
phospholipid_human.csv : 0.01 %
ckd.csv : 0.01 %
angiotensin_human.csv : 0.01 %
iron_deficiency.csv : 0.01 %
immune_response.csv : 0.01 %
cortisol.csv : 0.01 %
human_semen.csv : 0.01 %

and

*********Topic : ugt1a9 ***************
ugt1a9.csv : 99.80 %
ugt1a1.csv : 12.67 %
glucuronidation.csv : 7.05 %
udpgluc.csv : 5.78 %
pxr.csv : 0.91 %
car.csv : 0.48 %
cyp1a2.csv : 0.47 %
cyp3a4.csv : 0.41 %
nqo1.csv : 0.36 %
gilberts.csv : 0.33 %
cyp2d6.csv : 0.21 %
hydrolysis.csv : 0.18 %
cyp2e1.csv : 0.17 %
sulfotransferase.csv : 0.16 %
p450.csv : 0.16 %
bilirubin.csv : 0.15 %
conjugation.csv : 0.15 %
sulfation.csv : 0.14 %
enterohepatic_circulation.csv : 0.14 %
detoxification.csv : 0.14 %
fmo3.csv : 0.13 %
p450oxidoreductase.csv : 0.13 %
nrf2.csv : 0.12 %
cyp1a1.csv : 0.11 %
resveratrol.csv : 0.11 %
cyp1b1.csv : 0.11 %
esr1.csv : 0.07 %
rxr.csv : 0.06 %
oxidation.csv : 0.06 %
ginkgo.csv : 0.06 %
hepatocytes.csv : 0.04 %
nad.csv : 0.04 %
hepatotoxicity.csv : 0.04 %
finasteride.csv : 0.04 %
dht.csv : 0.03 %
pregnenolone.csv : 0.03 %
steatohepatitis.csv : 0.03 %
sirt1.csv : 0.03 %
isotretinoin.csv : 0.03 %
beta-alanine.csv : 0.02 %
n-acetyltransferase.csv : 0.02 %
nadph.csv : 0.02 %
mthfr.csv : 0.02 %
glutathione_stransferase.csv : 0.02 %
fluoroquinolone.csv : 0.02 %
curcumin.csv : 0.01 %
nafld.csv : 0.01 %
biliary_cirrhosis.csv : 0.01 %
niacin.csv : 0.01 %
liver_injury.csv : 0.01 %
triiodothyronine_levels.csv : 0.01 %
thioredoxin.csv : 0.01 %
oxidative_stress_protection.csv : 0.01 %
er_stress.csv : 0.01 %
liver_disease.csv : 0.01 %
protease_inhibitor.csv : 0.01 %
glycosylation.csv : 0.01 %
serotonin_levels.csv : 0.01 %

 

[Gondwanaland]

Thank you so much, Mario! I will study those list carefully and try to figure out the impact of each item, for instance

isotretinoin.csv : 0.03 %
beta-alanine.csv : 0.02 %

I suppose isotretinoin can have an impact similar to finasteride, but he could benefit from taking beta-alanine (as well as Ginkgo and Resveratrol), right?

 

[mariovitali]

Thank you so much, Mario! I will study those list carefully and try to figure out the impact of each item, for instance

I suppose isotretinoin can have an impact similar to finasteride, but he could benefit from taking beta-alanine (as well as Ginkgo and Resveratrol), right?

Exactly right

You just have to understand the context (i.e Resveratrol is beneficial or *not* beneficial for UGTs, or it is simply being mentioned)

If i had more time i would have the software make that automatically but...

 

[Violeta]

Here's an interesting case of liver injury due to copper overload in dogs

Must Read: Copper Storage

The short story is that dog food had been supplemented with too much copper, which likely lead to the deaths of a number of dogs. Further down the thread (post #10), we find that someone has given their dog TUDCA with good results.



For those that believe liver injury is a component, or even basis, of our disease, it is natural to ask exactly how did the liver injury occur. There's a long list of possibilities, including this one: copper overload.

Copper storage is a very good issue to look into. Not only copper, but iron storage, too.

http://www.sciencedirect.com/science/article/pii/S1568163704000121

A simple solution is B2, (FMN), which had been brought into the discussion by ppodhjaski for a different benefit.

 

[Violeta]

Hi @jump44,

In the case of primary biliary cirrhosis, which is an autoimmune condition, treatment does include UDCA as discussed in the Wikipedia entry, but it is controversial.

Most of the patients (>90%) have anti-mitochondrial antibodies (AMAs) against pyruvate dehydrogenase complex(PDC-E2), an enzyme complex that is found in the mitochondria



An AMA test can be used to help diagnose.

That is very good information, @skwag. When there is an antibody to an enzyme, it always seems to be a tricky situation. Statins can cause autoimmune disease polymyositis with an autoantibody to HMG-CoA. If you ever see a way to correct the situation, please let me know.

In the case of statins we of course know that statins are made to affect HGM-CoA, but I don't know if there is information about how it causes antibodies.

@jump44, I was looking through your other posts to see if you took a medication that was meant to attack that specific enzyme, but I don't see anything.

Some people consider autoimmunity to be autotoxicity, although lately I have seen information about aseptic autoimmunity, and the polymyositis caused by statins is in that group.
But I am wondering that since the worsening of your condition started without taking a medication if it has to do with a bacteria. This is from wikipedia and about the enzyme. See how it's found in bacteria? Cross reactive? I've seen that with respect to viruses. Unless there is a virus involved, too???

"PDC is a large complex composed of multiple copies of 3 or 4 subunits depending on species.

Gram-negative bacteria[edit]
In Gram-negative bacteria, e.g. Escherichia coli, PDC consists of a central cubic core made up from 24 molecules of dihydrolipoyl transacetylase (E2). Up to 24 copies of Pyruvate dehydrogenase (E1) and 12 molecules of dihydrolipoyl dehydrogenase (E3) bind to the outside of the E2 core.[1]

Gram-positive bacteria and eukaryotes[edit]
In contrast, in Gram-positive bacteria (e.g. Bacillus stearothermophilus) and eukaryotes the central PDC core contains 60 E2 molecules arranged into an icosahedron.

Eukaryotes also contain 12 copies of an additional core protein, E3 binding protein (E3BP). The exact location of E3BP is not completely clear. Cryo-electron microscopy has established that E3BP binds to each of the icosahedral faces in yeast.[2] However, it has been suggested that it replaces an equivalent number of E2 molecules in the bovine PDC core.

Up to 60 E1 or E3 molecules can associate with the E2 core from Gram-positive bacteria - binding is mutually exclusive. In eukaryotes E1 is specifically bound by E2, while E3 associates with E3BP. It is thought that up to 30 E1 and 6 E3 enzymes are present, although the exact number of molecules can vary in vivo and often reflects the metabolic requirements of the tissue in question.
PDC is a large complex composed of multiple copies of 3 or 4 subunits depending on species.

 

[mariovitali]

@skwag @Violeta

*********Topic : pyruvate dehydrogenase complex ***************
ndufs7.csv : 5.26 %
lipoic_acid.csv : 3.53 %
biliary_cirrhosis.csv : 2.91 %
pyruvate_carboxylase.csv : 2.22 %
acetyl-coa.csv : 2.06 %
thiamine.csv : 1.34 %
cholestasis.csv : 0.65 %
l_carnitine.csv : 0.60 %
pantethine.csv : 0.45 %
pgc1.csv : 0.42 %
fad.csv : 0.38 %
sirt3.csv : 0.37 %
flavoprotein.csv : 0.36 %
acetyl_coa_carboxylase.csv : 0.33 %
acetylation.csv : 0.32 %
nadh_dehydrogenase.csv : 0.31 %
exercise_intolerance.csv : 0.30 %
ppp.csv : 0.26 %
mitochondrial_dysfunction.csv : 0.24 %
nad.csv : 0.23 %
propionyl_coa_carboxylase.csv : 0.23 %
o-glcnacylation.csv : 0.19 %
oxidation.csv : 0.19 %
cofactor.csv : 0.18 %
coenzymeq10.csv : 0.18 %
hyperammonemia.csv : 0.14 %
choline_deficiency.csv : 0.12 %
n-acetyltransferase.csv : 0.11 %
liver_disease.csv : 0.11 %
tocotrienol.csv : 0.10 %
pantothenic_acid.csv : 0.10 %
phosphorylation.csv : 0.09 %
redox_regulation.csv : 0.09 %
redox_cofactor.csv : 0.09 %
steatohepatitis.csv : 0.07 %
peroxynitrite.csv : 0.07 %
glutaredoxin.csv : 0.07 %
creatine_supplementation.csv : 0.06 %
glutamine.csv : 0.06 %
sod2.csv : 0.06 %
l-cysteine.csv : 0.06 %
oxalates.csv : 0.06 %
d_aminoacid_oxidase.csv : 0.06 %
glutamate.csv : 0.06 %
riboflavin.csv : 0.06 %
nitration.csv : 0.05 %
excitotoxicity.csv : 0.05 %
urea_cycle.csv : 0.05 %
pdi.csv : 0.05 %
biotin.csv : 0.05 %
enterohepatic_circulation.csv : 0.05 %
sod1.csv : 0.05 %
nqo1.csv : 0.05 %
hexosamine.csv : 0.04 %
nadph.csv : 0.04 %
glutathione_stransferase.csv : 0.04 %
monosodium_glutamate.csv : 0.04 %
serca.csv : 0.04 %
heat_shock_protein.csv : 0.04 %
hepatocytes.csv : 0.04 %
fmn.csv : 0.03 %
rxr.csv : 0.03 %
chaperones.csv : 0.03 %
phenylketonuria.csv : 0.03 %
peroxiredoxin.csv : 0.03 %
sulfur.csv : 0.03 %
sirt1.csv : 0.03 %
ros.csv : 0.03 %
p5p.csv : 0.03 %
detoxification.csv : 0.03 %
methionine.csv : 0.03 %
pbmc.csv : 0.02 %
choline.csv : 0.02 %
niacin.csv : 0.02 %
calcium_homeostasis.csv : 0.02 %
reduced_glutathione.csv : 0.02 %
tau.csv : 0.02 %
astrocytes.csv : 0.02 %
immune_response.csv : 0.02 %
oxidative_stress_markers.csv : 0.02 %
insulin_resistance.csv : 0.02 %
liver_injury.csv : 0.02 %
redox_potential.csv : 0.02 %
taurine.csv : 0.02 %
ebv.csv : 0.02 %
nrf2.csv : 0.02 %
h2o2.csv : 0.02 %
xanthine_oxidase.csv : 0.02 %
cyp2d6.csv : 0.02 %
catalase.csv : 0.02 %
stat1.csv : 0.02 %
bilirubin.csv : 0.02 %
cfs.csv : 0.02 %
pregnenolone.csv : 0.01 %
resveratrol.csv : 0.01 %
ubiquitination.csv : 0.01 %
acetylcholine.csv : 0.01 %
hydrolysis.csv : 0.01 %
nac.csv : 0.01 %
nmda.csv : 0.01 %
caspase_human.csv : 0.01 %
thioredoxin.csv : 0.01 %
inositol.csv : 0.01 %
hsp70.csv : 0.01 %
oxidative_stress_protection.csv : 0.01 %
inflammatory_response.csv : 0.01 %
butyrate.csv : 0.01 %
monoamine_oxidase.csv : 0.01 %
molybdenum.csv : 0.01 %
il_10.csv : 0.01 %
liver_regeneration.csv : 0.01 %
probiotics.csv : 0.01 %
hydroxysteroid_dehydrogenase.csv : 0.01 %
bile_acid.csv : 0.01 %
amyloid.csv : 0.01 %
hepatotoxicity.csv : 0.01 %
gut.csv : 0.01 %
l-arginine.csv : 0.01 %
hgh.csv : 0.01 %
conjugation.csv : 0.01 %

 

[Violeta]

That is very good information, @skwag. When there is an antibody to an enzyme, it always seems to be a tricky situation. Statins can cause autoimmune disease polymyositis with an autoantibody to HMG-CoA. If you ever see a way to correct the situation, please let me know.

In the case of statins we of course know that statins are made to affect HGM-CoA, but I don't know if there is information about how it causes antibodies.

@jump44, I was looking through your other posts to see if you took a medication that was meant to attack that specific enzyme, but I don't see anything.

Some people consider autoimmunity to be autotoxicity, although lately I have seen information about aseptic autoimmunity, and the polymyositis caused by statins is in that group.
But I am wondering that since the worsening of your condition started without taking a medication if it has to do with a bacteria. This is from wikipedia and about the enzyme. See how it's found in bacteria? Cross reactive? I've seen that with respect to viruses. Unless there is a virus involved, too???

"PDC is a large complex composed of multiple copies of 3 or 4 subunits depending on species.

Gram-negative bacteria[edit]
In Gram-negative bacteria, e.g. Escherichia coli, PDC consists of a central cubic core made up from 24 molecules of dihydrolipoyl transacetylase (E2). Up to 24 copies of Pyruvate dehydrogenase (E1) and 12 molecules of dihydrolipoyl dehydrogenase (E3) bind to the outside of the E2 core.[1]

Gram-positive bacteria and eukaryotes[edit]
In contrast, in Gram-positive bacteria (e.g. Bacillus stearothermophilus) and eukaryotes the central PDC core contains 60 E2 molecules arranged into an icosahedron.

Eukaryotes also contain 12 copies of an additional core protein, E3 binding protein (E3BP). The exact location of E3BP is not completely clear. Cryo-electron microscopy has established that E3BP binds to each of the icosahedral faces in yeast.[2] However, it has been suggested that it replaces an equivalent number of E2 molecules in the bovine PDC core.

Up to 60 E1 or E3 molecules can associate with the E2 core from Gram-positive bacteria - binding is mutually exclusive. In eukaryotes E1 is specifically bound by E2, while E3 associates with E3BP. It is thought that up to 30 E1 and 6 E3 enzymes are present, although the exact number of molecules can vary in vivo and often reflects the metabolic requirements of the tissue in question.
PDC is a large complex composed of multiple copies of 3 or 4 subunits depending on species.

Later in the wiki article it explains how a pathogen causes autoimmune biliary cirrhosis.

"In 2003 it was reported that an environmental Gram negative alphabacterium — Novosphingobium aromaticivorans[22] was strongly associated with this disease. Subsequent reports appear to have confirmed this finding suggesting an aetiological role for this organism.[23][24][25] The mechanism appears to be a cross reaction between the proteins of the bacterium and the mitochondrial proteins of the liver cells.[26] The gene encoding CD101 may also play a role in host susceptibility to this disease.[27]"

 

[gefinauser]

Yo @skwag, @jump44. Fellow PFS/CFS sufferer here. I'm on the same boat as mariovitali.
the liver focus helping healing injury interests me greatly... I may have had a similar experience recently and perhaps this liver focus helps it as well. We'll see in the future.

@jump44 , my condolences of using fq abx, i did the same them too. have you done by any chance this special prostatitis drainage treatment that required FQ's by doc?

@ahmo, this is actually the real reason I wanted to post: do you have Alpha GPC, Inositol, TUDCA, FMN, just like mariovitali has?
if yes, can you please muscle test out how strong you test for them seperately/alone... TUDCA, FMN
and then Alpha-GPC -Inositol together (so ask yourself that "if I take x and y together, then I need to take x/y for 1/2/etc pills" etc).
I figured I can't talk with you in pm but perhaps this way you get notified for this idea. I don't know anyone else who muscle tests & who has access to methylation supps.

 

[ahmo]

Re liver: Most of this thread is just beyond the edge of my comprehension. But these last posts referring to liver have finally hit the mark. I'm taking this opportunity to note that last year was one of ongoing detox and attending to my liver. Key to this was coffee enemas. I've noticed this is a red flag to some people. I'm quite clear that my current level of well being is thanks to CEs. And to further note that I now use them less than monthly, and my bowel health is excellent.

this is actually the real reason I wanted to post: do you have Alpha GPC, Inositol, TUDCA, FMN, just like mariovitali has?
if yes, can you please muscle test out how strong you test for them seperately/alone... TUDCA, FMN
and then Alpha-GPC -Inositol together (so ask yourself that "if I take x and y together, then I need to take x/y for 1/2/etc pills" etc).
I figured I can't talk with you in pm but perhaps this way you get notified for this idea. I don't know anyone else who muscle tests & who has access to methylation supps.

I haven't tried Alpha GPC yet, I'm planning to soon. I've been using citicoline, to good results.

I used to take extra inositol, but now only the 12.5mg in my B Complex.

I'm not using Tudca. I've found that if I wanted I could get an rx for UDCA, but the little I read about it, I'm not sure it's worthwhile. I'd have to revisit it, since I can't recall my reasoning.

FMN: I've just had an excellent breakthrough her. I'd been taking 1x 18.5mg sublingual , + there's 25mg r5p in the B comp. This past week I've experimented w/ transdermal FMN. I've now created a delivery system that's letting me use 1/2 tha amount I had been sublingually. And I've gone to using it twice a day. So, 1/4 tab AM and Midday. Will be switching to capsule form of r5p next, hopefully there's no difference between r5p and FMN.

How I test: I just check each supp w/ my body. I love self-testing because my ability to hold things in my working memory is so compromised. To try to do this in the way you've suggested, would be like asking a millipede how it manages to walk with all those feet. As soon as asked, he can no longer move, paralyzed by trying to work out how it works. And asking my body would have no bearing on what the answers would be for your body. Feel free to pm me if you want.

 

[mariovitali]

@skwag , @Gondwanaland , @jump44, @gefinauser

Please have a look at the following Genes :

Cholestasis

rs2273061 Risk A - JAG1
rs35724 Risk C - NR1H4

Bile Acids

CYP7A1
rs3808607 Risk T
rs3824260 Risk G

CYP8B1
rs3732860 (Risk C)


Association Analysis for CYP7A1 : Notice how car,pxr, bile_acid,enterohepatic circulation are associated with CYP7A1

car= constitutive androstane receptor
fxr = farnesoid x receptor

 

[skwag]

First two homo, second two hetero.

What are you basing the risk on? The research I could find seemed a little weak.

 

[mariovitali]

@skwag

I take the Risk from here (example for JAG1) :

https://www.pharmgkb.org/variant/rs2273061

Please note that i added one more gene CYP8B1 at my post above.

Regarding the research being weak : Can you look at the research behind CYP8B1 for example and let me know what you think?

 

[mariovitali]

Dear All,

Please find attached a new version of the document. Several genes for Bile Acids, Cholestasis, Sulfation have been added.

 

[ahmo]

Cholestasis

rs2273061 Risk A - JAG1 AG
rs35724 Risk C - NR1H4 CC

Bile Acids

CYP7A1
rs3808607 Risk T TT
rs3824260 Risk G GG

CYP8B1
rs3732860 (Risk C) TT

 

[skwag]

@skwag

I take the Risk from here (example for JAG1) :

https://www.pharmgkb.org/variant/rs2273061

Please note that i added one more gene CYP8B1 at my post above.

Regarding the research being weak : Can you look at the research behind CYP8B1 for example and let me know what you think?

I couldn't see any research on the link you posted. It's possible my browser is not displaying the page correctly. Is there a particular paper or two that you are basing the risk on?

The CYP8B1 SNP is not on my chip. There are couple papers regarding this mutation at SNPedia. They both appear to be on a small number of Chinese subjects. The P-values are high, around .025 . I'd consider this pretty weak evidence of risk.