Dq2/other Low Risk Gene -- Help With Prometheus Lab Results?

[Chakra2]

I just got a call from the nurse at my GI doc (not a celiac specialist). She said that my genetic test results from Prometheus lab showed that I have a DQ2/other low-risk gene which puts me at a very low risk for celiac (level two out of 8 risk levels). Does this mean I have a DQ2 or not? Is it possible to develop celiac with those results or not? Anyone else get this result?

I went gluten free for other reasons 5 months ago so my bloodwork was negative. I was hoping the genetic results would magically reveal answers to me! But the nurse who called couldn't even tell me for sure if I have a DQ2 or not. I hope someone can help me interpret this a little.

Thanks!

Chakra2

[ravenwoodglass]

If you can get a hard copy of the results and post them here someone will be able to answer your question. Please note that having or not having the most common celiac related genes is not diagnostic.

Have you gotten relief from the gluten free diet and are you following it strictly. If the answers to both questions are yes then you really do already have your answer, IMHO.

[Chakra2]

I won't have the hardcopy for a few more days, but I think I understand a little more. I have one DQ2 gene and one other gene (that is neither DQ2 nor DQ8). Are there folks here who have a similar genetic result (one DQ2 gene) and have actually developed celiac?

I do get great results on the diet but I want to know a little more about the genetic risk results too.

[Skylark]

You need to know which DQ2 subtype, although you probably have DQ2.2 or 2.3 if Prometheus put you in a low risk group. Yes, it's possible to develop celiac with DQ2.2; it's just less common than with DQ2.5 or DQ8 so the gene is considered low risk. "Low risk" things happen all the time. Just ask BP.

Remember that lab tests are only pieces of paper. If you feel better off gluten, don't eat the stuff and don't worry about it.

[Jestgar]

Please note that having or not having the most common celiac related genes is not diagnostic.

I just want to emphasize what RWG said. These genes are associated with Celiac Disease. They are neither necessary, nor sufficient to cause the disease.

THERE HAVE BEEN NO GENES IDENTIFIED THAT ARE SHOWN TO CAUSE CELIAC DISEASE. Don't spend a lot of time getting caught up in the details that only tell you probabilities.

[ravenwoodglass]

I won't have the hardcopy for a few more days, but I think I understand a little more. I have one DQ2 gene and one other gene (that is neither DQ2 nor DQ8). Are there folks here who have a similar genetic result (one DQ2 gene) and have actually developed celiac?

I do get great results on the diet but I want to know a little more about the genetic risk results too.

Please please as Jestgar said do not get hung up on the genes. There is much that is not known about celiac and the most important thing is how well you have responded to the diet not what genes you have. I would hate to see you give up the diet that is working well for you based on a science that is far from completely conclusive. I had that happen in my own family and believe me that is a tragedy.

I have neither DQ2 or DQ8 and have been definately diagnosed with celiac. And the damage done was severe and life changing.

[ravenwoodglass]

You need to know which DQ2 subtype, although you probably have DQ2.2 or 2.3 if Prometheus put you in a low risk group. Yes, it's possible to develop celiac with DQ2.2; it's just less common than with DQ2.5 or DQ8 so the gene is considered low risk. "Low risk" things happen all the time. Just ask BP.

Remember that lab tests are only pieces of paper. If you feel better off gluten, don't eat the stuff and don't worry about it.

It is possible to develop celiac with a large number of different genes. To rely on gene testing to tell you whether or not you can eat gluten is IMHO as big mistake as relying on the blood and biopsy for definate diagnosis or exclusion. My doctors relying on the blood work cost me many years, a great deal of pain and permanent damage. Doctors relying on someone having DQ2 or DQ 8 as a certainty that someone does or does not have celiac is costing my DD her health. Gene testing is not proof one way or the other.

As you said the most important thing is how someone responds to the diet, not what gene they carry.

[Skylark]

THERE HAVE BEEN NO GENES IDENTIFIED THAT ARE SHOWN TO CAUSE CELIAC DISEASE. Don't spend a lot of time getting caught up in the details that only tell you probabilities.

Waitaminute. That's too glib. The DQ2.5 studies point to a very clear mechanism for celiac disease and there is a DQ2.5 dosage effect where homozygotes have a higher risk than DQ2.5 trans or heterozygotes. I think it is completely fair to call HLA-DQ2.5 a "celiac gene".

The research is also very clear that DQ2.5 is neither necessary nor sufficient for celiac, similar to the well-known cancer genes like P53 and BRCA1 or BRCA2. Other things have to happen to the person to have induction, and like cancer, you can get the disease with different genetics. Diseases like sickle cell anemia or CF where homozygous people have disease 100% of the time are actually relatively rare because of the complexity of the human body.

[Jestgar]

Diseases like sickle cell anemia or CF where homozygous people have disease 100% of the time are actually relatively rare because of the complexity of the human body.

Without going into a big huge discussion, this is the bottom line.

I have not seen evidence showing that the presence of any single gene (hetero- or homozygous) is required to develop celiac disease, nor have I seen evidence showing that only people with a single gene develop celiac disease.

This is, at best, a polygenic disease. I won't argue that some of the HLA types have been shown to be able to be able to destroy the lining of the gut after some protein interactions with gliadin that lead to the molecule recognizing self as foreign (been a long time since I've read these, I'm paraphrasing badly), HOWEVER, why do some people with the predisposing genetic fingerprint never develop this destructive behavior? Is there a triggering protein? Triggering virus? Some other gene required that has not yet been identified? Some combination of these?

'Associated' is not good enough for me to accept any of the HLA combinations as 'Celiac genes'. If you can develop celiac disease without having any of these genes, they aren't worth giving the importance that many people feel inclined to give them.

What are the stats on having BRCA1 or 2 and never getting breast/ovarian cancer?

[Chakra2]

Thanks to everyone for the responses. In theory I agree that I should just trust my diet results and move on. I think that in other parts of my life I've been pretty comfortable forging my own path without looking to outside sources for validation. But this process of going from feeling fine to feeling sick to feeling fine again has shredded my confidence somehow. I'm still trying to figure out why that is before I answer my own question in another thread about what my "gut" is trying to tell me!

On a more practical level, I am concerned about symptoms in parents, siblings and especially my toddler so I was hoping I could get some persuasive scientific info to help start discussions with family and pediatrician.

Laughed out loud at the BP remark--I totally see your point!

[Skylark]

'Associated' is not good enough for me to accept any of the HLA combinations as 'Celiac genes'. If you can develop celiac disease without having any of these genes, they aren't worth giving the importance that many people feel inclined to give them.

What are the stats on having BRCA1 or 2 and never getting breast/ovarian cancer?

According to the National Cancer Center, normal lifetime risk for breast cancer is 12%, while that of women with BRCA1 or BRCA2 is 60%. Normal lifetime risk for ovarian cancer is 1.4%, while with one of the genes it's estimated to be 15%-40%.

They note "Because family members share a proportion of their genes and, often, their environment, it is possible that the large number of cancer cases seen in these families may be due in part to other genetic or environmental factors. Therefore, risk estimates that are based on families with many affected members may not accurately reflect the levels of risk for BRCA1 and BRCA2 mutation carriers in the general population."

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Sounds a lot like we say about HLA-DQ and celiac, doesn't it? The highest risk factor for celiac is having a first degree relative with the disease.

The big Prometheus study pretty clearly shows that people with DQ2.5 or DQ8 and symptoms or an affected family member are at substantially elevated risk for having anti-endomysial IgA compared to those without a gene. Someone like the new member who was confused about homozygous DQ2.5 would have an impressive 28% risk of testing positive for anti-EMA, which is far above the population risk. Of the 4283 people without DQ2 or DQ8, only 0.16% had anti-EMA.

Open Original Shared Link

I know people have trouble interpreting risk numbers (as is evidenced by fear of air travel) but that is not a reason to discard or minimize useful information from genetic tests. Sometimes that's the only solid information we can get without destroying our bodies with gluten and Prometheus has gone to great expense and effort to do that huge study to help people interpret their results. What we have to avoid is the mistake of saying that there is zero risk associated with HLD-DQ types other than DQ2 or DQ8, as Ravenwoodglass keeps shouting from the local mountaintop!

Edit: @Chakra2 after glancing at the Prometheus paper I just linked to you really DO need to find out which DQ2 you have because I think they might be talking about DQ2.5. If I had a DQ2.5 gene and a child, I might get him tested and I would certainly be watching carefully for gluten reactions. I am perhaps more convinced by the DQ2/DQ8 research than some folks around here. (Which is OK.)

[melblondin]

If I had to guess, I'd say you have DQ 2.2 because I also did the Prometheus testing and mine came back as "DQ2 heterozygous," which put me in a "high" risk category. At the bottom of my report where it lists what alleles were detected it stated: DQ2.5 (HLA DQA1*05:DQB1*0201) and other non-risk alleles. I'm assuming the only thing that separates the "DQ2 Heterozygous" and the "DQ2/other low risk gene" categories are the subtypes. Please correct me if I'm wrong though!!

[ravenwoodglass]

What we have to avoid is the mistake of saying that there is zero risk associated with HLD-DQ types other than DQ2 or DQ8, as Ravenwoodglass keeps shouting from the local mountaintop!

And Ravenwoodglass will continue to do so. Please don't take it personally. I don't want what happened to me and my family to happen to anyone else. Unfortunatly not all doctors are up on the other genes that can be associated. After what happened with my daughter at one of the most well respected hospitals in the country I do feel the need. Hopefully someday I won't have to mention it any more but as I know you are aware research is a slow process especially with a disease that is controlled by diet alone. At least in this pharmacologic society.

[Jestgar]

They note "Because family members share a proportion of their genes and, often, their environment, it is possible that the large number of cancer cases seen in these families may be due in part to other genetic or environmental factors. Therefore, risk estimates that are based on families with many affected members may not accurately reflect the levels of risk for BRCA1 and BRCA2 mutation carriers in the general population."

And presumably people who have tested positive are told of their increased risk, not, as frequently happens on this board, told what course their cancer will take based on their genes.

If you test positive for any of the HLA haplotypes associated with celiac disease, you have an increased risk. There are no data that I know of that say you will have celiac disease with certain HLA haplotypes, nor that you will not have celiac disease without them, nor that with certain haplotypes you will have a predominance of neuro symptoms or any other type of symptom.

These genes have not been shown to cause celiac disease, and therefor, knowing whether or not you carry them only tells you your relative risk, not that you have the disease.

[Skylark]

And Ravenwoodglass will continue to do so. Please don't take it personally. I don't want what happened to me and my family to happen to anyone else.

I know it's not personal. I mentioned you as a positive nod. I completely understand as I'm shouting just as loudly about 15 years of psych misdiagnoses, with exactly the same hopes. If even one person with chronic GI trouble and depression/fatigue gets diagnosed with celiac instead of put on Prozac and shuttled off to the psychiatrist with a pat on the head, I've succeeded.

[ravenwoodglass]

I know it's not personal. I mentioned you as a positive nod. I completely understand as I'm shouting just as loudly about 15 years of psych misdiagnoses, with exactly the same hopes. If even one person with chronic GI trouble and depression/fatigue gets diagnosed with celiac instead of put on Prozac and shuttled off to the psychiatrist with a pat on the head, I've succeeded.

Yea I had over 40 years of their 'it's all in your head' diagnoses myself. Even with brain lesions found on an MRI and a flat electromylogram on my right leg I was still told that I was just 'depressed' here's a prozac. I even had a neuro tell me that I was sick because I wanted to be sick. I don't think I will ever personally trust doctors for anything again.

[hermpal]

wish there was just a simple yes or no way to find out if we have celiac disease. If we don't have celiac we have something because none of us feel like 100 % healthy people. I tried for 7 months to explain this to a G.I. and was told he would do surgery on my stomach or give me another anti depressant. Very worthless test and really no thought put into the info I was giving him. Second G.I. listened and even examined me and ordered the test for celiac. Of course her mom has it so she had that going in her favor as what to look for. Gluten free for 1 mo. Still have nausea and moody but do have some days I can feel my oldself coming back. The nausea is the worse. Have lost 8 lbs in the mo and that makes me feel better but still hard to find a place to eat out..Husband very supportive but Thanksgiving was very stressful. Not know if cross contamiation was possible. Have to learn more each day.

[lcarter]

I, too, recently gene tested with Prometheus labs and was told that I am negative for both DQ2 + DQ8 - so have an "Extremely Low" chance of developing Celiac Disease. Well, I am, for sure, sensitive to wheat, rye, barley and oats; also extremely Dairy Intolerant to both factions [lactose + protein], plus have Fructose Malabsorption. In any event, a gluten-free diet has helped me immensely! Wither it is true Celia Disease, Crohn's [inflammatory Bowel Disease], or the fructans, rather than the gluten, in the grains that I am reacting to, is an unanswerable question. But, does it really matter when the diet works? I have classic GI symptoms when I get off the gluten free diet.