The power and pitfalls of omics part 2: epigenomics, transcriptomics and ME/CFS
Simon McGrath concludes his blog about the remarkable Prof George Davey Smith's smart ideas for understanding diseases, which may soon be applied to ME/CFS.
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IDO2, Autoimmune Issues, and Cancer

Discussion in 'Genetic Testing and SNPs' started by ppodhajski, Aug 23, 2015.

  1. ppodhajski

    ppodhajski

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    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
     
    merylg likes this.
  2. skwag

    skwag Senior Member

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    Hi ppodhajski,

    Dumb question: Is it the C or T that reduces the IDO2 activity?
     
  3. ppodhajski

    ppodhajski

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    Chapel Hill, NC
    I think it is T. It looks like all the research says it is a C to T switch. But I am not 100%. I am CT for it.
     
  4. skwag

    skwag Senior Member

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    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!
     
  5. ppodhajski

    ppodhajski

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    Chapel Hill, NC
    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?
     
  6. Valentijn

    Valentijn WE ARE KINA

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    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.
     

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