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IDO2, Autoimmune Issues, and Cancer

ppodhajski

Senior Member
Messages
243
Location
Chapel Hill, NC
Curious if some of you, specifically the ones with autoimmune issues, can look up this SNP
IDO2 R248W
https://www.23andme.com/you/explorer/snp/?snp_name=rs10109853

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4238401/

IDO degrades tryptophan to produce kynuremic acid and finaly NAD (Niacin). And it uses iron as a cofactor
http://www.uniprot.org/uniprot/Q6ZQW0

I am heterozygous for this SNP; CT and apparently it means a 90% reduction in enzyme activity! Which means I might need more iron, which is also interesting since I am a hemochromotosis carrier.

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0115848
The finding that one of the IDO2 minor allele variants conferred CD risk is provocative, particularly given that this SNP, rs10109853 (R248W), confers a 90% reduction in enzymatic activity

http://www.researchgate.net/publica...ase_2_genotype_with_specific_immune_responses
Interestingly, we found a higher number of immune responses against
IDO2 in patients homozygous for the 248W giving reduction in IDO2 activity compared with the 248R. Hence,
spontaneous immune responses against IDO2 seem to be correlated with reduced enzymatic activity of IDO2.


Apparently, however, my SNP with the rare allele is protective against cancer and chron's.
http://pharmaceuticalintelligence.c...ostasis-of-immune-responses-for-good-and-bad/
Human tumor cells constitutively produce TDO also contributes to production of Kyn as an endogenous ligand of the AhR (75; 27). Degradation of tryptophan by IDO1/2 in tumors and tumor-draining lymph nodes occur. As a result, there are animal studies and Phase I/II clinical trials to inhibit the IDO1/2 to prevent cancer and poor prognosis (NewLink Genetics Corp. NCT00739609, 2007).

But maybe this is why iron could play a role in cancer?
http://www.ncbi.nlm.nih.gov/pubmed/8664805

Here is a long article:
http://jdc.jefferson.edu/cgi/viewcontent.cgi?article=1067&context=mifp
 

skwag

Senior Member
Messages
222
I'm TT. I don't have any diagnosed autoimmune conditions, but like a lot of people whose symptoms seems to flare, I am suspicious of an autoimmune component. As far as I know, my family has no history of cancers. It is an interesting topic!
 

ppodhajski

Senior Member
Messages
243
Location
Chapel Hill, NC
I'm TT. I don't have any diagnosed autoimmune conditions, but like a lot of people whose symptoms seems to flare, I am suspicious of an autoimmune component. As far as I know, my family has no history of cancers. It is an interesting topic!

Yes, no one gene will cause issues, you need to look at this gene and how it relates to the the body as a whole. The flaring is interesting to me, almost like you are more sensitive?
 
Messages
15,786
IDO and IDO2 are two different genes which both perform the same function. This isn't particularly uncommon for genes - basically sometimes there is a back-up which will keep everything operating normally if the other one fails. I have a similar issue with recycling a B vitamin, though in that case it's a rare mutation. But the other gene which also recycles that vitamin functions normally and prevents any problems from occurring.

So even though significant IDO2 missense and nonsense mutations are extremely common, they don't cause any problems because IDO is functioning normally.
 

aquariusgirl

Senior Member
Messages
1,732
Interesting. I am C/T for R235W or rs 10109853. So is my mom & she is heterozygous for one of the big 3 hemochromatosis SNPs.
 

frozenborderline

Senior Member
Messages
4,405
IDO and IDO2 are two different genes which both perform the same function. This isn't particularly uncommon for genes - basically sometimes there is a back-up which will keep everything operating normally if the other one fails. I have a similar issue with recycling a B vitamin, though in that case it's a rare mutation. But the other gene which also recycles that vitamin functions normally and prevents any problems from occurring.

So even though significant IDO2 missense and nonsense mutations are extremely common, they don't cause any problems because IDO is functioning normally.
according to the recent robert phair metabolic trap theory, this is not necessarily true because IDO1 is substrate-inhibited and doesn't work once tryptophan levels are high
 

Seven7

Seven
Messages
3,444
Location
USA
T / T what does it mean do I have it mutated? Diagnosed w Colitis, POTs and CFS
 

stetson28

If it aint broke don't fix it...but.
Messages
49
Location
Richmond Virginia
Is valentijn no longer on the Phoenix Rising boards? He/she used to maintain a database of rare and unusual snp's and how they correlate statistically to the general populace and the participants on Phoenix Rising.
I had a couple of snaps I wanted to review and didn't know if there was anyone else who was able to? Thanks, Thomas
 
Messages
99
Is valentijn no longer on the Phoenix Rising boards?

Earlier this year, I noticed that activity across all of phoenixrising seemed lower than usual, and genetic discussion was particularly reduced. I searched forums for a few specific usernames, and realized there'd been a change behind the scenes in 2017. Search "Posted by Member" for "Valentijn"and you'll see what I mean.

So now we have phoenixrising.me, and healthrising.org, and s4me.info... three different places to check instead of just one. :-/
 
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