Why is genetic testing not commonly used to distinguish UC vs CD?

[killcolitis]

My daughter has a dx of UC and is facing surgery if remicade doesn't work. We have tried to avoid surgery for the past four years due to our fear that it will end up being CD and we'll be down a colon and back on the meds. I was wondering since they now know which that certain genes are correlated with CD (and less so with UC) why is testing for these not standard practice at diagnosis or at least before surgery. I know promethius tests for some but they aren't very many. Our GI is a researcher working on IBD and genetics and she brushed off some of the promethius stuff. Any one have any ideas? Is this worth pursing?

 

[my little penguin]

Mainly because they have only identified a few of the genes for cd.
There are literally hundreds( at least that is the current thought).

I would not put much faith into a negative for one of the few known genes at this point.

 

[DanceMom]

We did have the Prometheus testing and it was one of the factors that led to diagnosis. Unfortunately, the test was extremely expensive (almost $700) and was not covered by insurance, even after multiple appeals. Our current GI didn't seem to put much faith in the test alone and admitted that there is plenty of room for error in the results.

 

[DustyKat]

I would have to agree with mlp. I don't think there is wider genetic testing because it is too unpredictable.

I can certainly see where you are coming from killcolitis and would find it overwhelming to be in the situation you are. Lord knows it is hard enough to make decisions when you have a clearcut diagnosis.

On a personal note, I would likely pursue whatever testing was available if I was able. It may provide me with some direction or it may be of no use to me whatsoever but at least in my own mind I would know I left no stone unturned.

I don't know if you have seen this article in the wiki but Judith has listed the genes that are implicated in some way to IBD:

http://www.crohnsforum.com/wiki/Genes-and-IBD

Thinking of you and hoping that Remicade is successful!

Dusty. xxx

 

[killcolitis]

We've had promethius and the serology indicated UC and one gene was more correlated with UC but our GI is a genetics researcher and said a lot of the population carried it and it wasn't a reason to change dx. We've just done the 23andme and a biggie for CD came up and a biggie for early onset UC. So, I'm totally confused and worried. I have an email into her and we'll see what she says I suppose.

 

[kiny]

The majority of people with those gene mutations linked to crohn's disease don't have crohn's disease.

The gene mutation is important for studies if you want to find the cause of crohn's disease, it gives researchers clues, but it's irrelevant for diagnostic purpose, since the percentage is so small, and the percentage of those people who actually get crohn's disease is even smaller. It would be like doing a diagnosis by shooting a dart blindfolded, you're going to miss most likely.

It happens in other diseases, like Huntington's disease. But crohn's disease gene are of academic importance, not diagnostic, there are way too many people with those mutations that don't have crohn's disease to make it relevant for diagnosis. The overwhelming majority of people with mutations in NOD2 and ATG16L1 don't have crohn's disease.

 

[killcolitis]

Thanks Kiny. I know these are polymorphisms and not mutations so are more "common" in the general population. But my question is in a known case of IBD which presents as UC but has CD correlated genes, does that warrant a second look at the diagnosis prior to colectomy or not? Complicating this is that the vast majority of genes associated are still unknown most likely so that would mean that the current odd ration given to specific findings aren't actually correct? Since I'm far from a statistician or an expert in genetics I'm trying to figure this out.
Is there diagnostic value in the above situation (dx UC vs CD)? Still waiting for our GI's response (she is a genetics expert so I'm very curious to know what she'll say).

 

[kiny]

Thanks Kiny. I know these are polymorphisms and not mutations so are more "common" in the general population. But my question is in a known case of IBD which presents as UC but has CD correlated genes, does that warrant a second look at the diagnosis prior to colectomy or not? Complicating this is that the vast majority of genes associated are still unknown most likely so that would mean that the current odd ration given to specific findings aren't actually correct? Since I'm far from a statistician or an expert in genetics I'm trying to figure this out.
Is there diagnostic value in the above situation (dx UC vs CD)? Still waiting for our GI's response (she is a genetics expert so I'm very curious to know what she'll say).

There's no diagnostic value in genetic screening, for UC or CD, or to differentiate between them. Differnentiating between UC and CD, should never be an issue with biopsies, they're distinctly different when they look at the crypts, crohn's disease is patchy transmural inflammation with distinguishable granuloma, it's very different from UC that's all over the intestine, and doesn't have any patches or those granuloma seen in CD.

The bigger problem is distinguishing intestinal TB from CD, because it's also patchy, it has similar granuloma, it's also transmural.

But there shouldn't be an issue to distinguish between UC and CD.

Here's the list of genetic predispositions between UC and CD, bigger bar means more susceptible, IL23 represent two different regions. If there are more genes, you are talking tiny percentages under 1% for all those genes outside of NOD2. You can't make a diagnosis based on them.

 

[kiny]

Complicating this is that the vast majority of genes associated are still unknown most likely so that would mean that the current odd ration given to specific findings aren't actually correct?

I don't think they're unknown. Crohn's disease isn't like huntington's disease where you can predict the disease, the genetic link in crohn's disease is extremely weak, even for NOD2. When immigrants move to Europe, they get increased rates of crohn's disease, without any genetic susceptibility, the environmental factor is much more important than the genetic, you need none of the genetic marker to get crohn's disease.

In Asia none of the people with crohn's disease even have the NOD2 variant.

NOD2 and ATG16L1 are interesting since they're related to autophagy, especially intracellular handling of bacteria, which makes AIEC, Listeria, MAP, Yersinia and others bacteria good candidates, but outside of that they serve no purpose. Even if someone had genetic susceptibility to get crohn's disease, what would you change, put them in a sealed box? It's pointless knowing from a patient perspective. I have had crohn's disease for 13 years now, the test to know if I have the NOD2 variant costs a few hundred dollar, I never asked to know, it's not going to help me, it has 0 diagnostic value, and would just make me worry more.

 

[killcolitis]

No, actually crohn's colitis and UC can be similar. 10% of adults with a solid UC dx actually end up with CD post colectomy (found either on colonic autopsy or by re-occurrence of disease in the SI later). It's much more common for children to present with colonic CD which appears to be UC. My daughter has classic UC on biopsy but because of her age of onset it's more likely that it is infact CD than in an adult. I wouldn't be bothering too much about this either other than the fact that we are facing colectomy and that is my last choice obviously if it's CD. She has Nod2, she has IL10 and a bunch of others.
Her GI says as you did that it's very complex and many healthy people are carriers of these genes. Of course, I understand that (they are polymorphisms, not mutations) but at the same time since she has an IBD I would like to know if these genetic findings ($99 through 23andme at the moment by the way) are in any way relevant to her diagnosis or not. Sorry, I'm not very clear about our situation most likely. Thanks for posting the genetic info. I'll look it over.

 

[kiny]

If you're really worried I would let someone else do the biopsies again if that's possible, and let a specialist do the histology. Genetic testing will just leave you in doubt, it won't clear up any questions, it will just create more.

 

[killcolitis]

She just had scopes and biopsies done which again indicate UC. So I guess you don't think having Nod2 is a biggie for a "UCer". Anyway, I'm in the process of hounding her GI about this atm. I'll post back about what she says in case this is of interest to anyone but me.

 

[DanceMom]

killcolitis - Are you referring to the IBD sgi Diagnostic test or the Crohn's Prognostic test? A had the Diagnostic test, and looking at her results I don't see any mention of the Nod2 (which the Prognostic tests for). The Diagnostic test combines serologic, genetic, and inflammation markers and aids in differentiating between IBD and non-IBD, and CD and UC.

A had 3 abnormal serology results, 3 genetic mutations detected, and 1 high inflammatory result. The results were never really broken down and explained to me, but the GI did state that it was one more piece to the puzzle that led to diagnosis.

 

[killcolitis]

NO, I'm not referring to promethius, though we've had that done too (the same one as you - serology indicative of UC, one genetic finding more indicative of CD and inflammatory snap shot, and you're right, no Nod2 for whatever reason).
I'm referring to a genome mapping service called 23andme and they used to be quite expensive but have recently reduced their prices so more people are using them. I actually did not even expect this finding, I had this done for my daughter for a completely different reason, so I'm a little shocked to say the least. I'm curious what our GI will say about this though. I've sent her the findings. No doubt it's very complicated but I want to know if this will affect her dx.