Genetic Testing

[Sam'sMom]

I'm wondering if anyone has done the genetic testing at home and if you had a chance to compare prices and have any wisdom on which ones are best and cheapest. Are you able to use any insurance if you order this for home use? Also, if your Dr. ordered the genetic test for you, I'm wondering if it was covered then, and how much. Mainly because I'll leave my Dr. out of the equation if it's not going to be covered anyway.

Thanks

[pricklypear1971]

I had my ND order genetic testing through LabCorp- my insurance (PPO) will include the labs in my deductible but I still pay for them (since I haven't met my deductible) at the contracted rate. Don't have the bill yet. They won't pay for my ND visits since they don't include ND's on the plan. They also include any RX my ND writes and a pharmacy fills under the plan at contracted rates.

I also ordered Enterolab genetic testing as part of a bundle and it's roughly $60. My insurance isn't including it in my deductible - not worth the hassle to argue about it.

[JoshB]

I would suggest checking out 23andme to do a full SNP map. You'll have to pay $99 up front and then sign up for their stupid "update service" at $5/month for a year.

[pricklypear1971]

HLA-DQA1Marker:rs2187668

Celiac Disease occurs only in people with certain versions of an immune system protein called HLA-DQ. HLA proteins are encoded by a set of genes on chromosome 6. Together the genes are referred to as the "HLA region." Proteins from the HLA family are involved in the immune system's recognition of invaders. They are responsible for presenting bits of foreign proteins to immune cells and triggering the cells to attack.

Functional HLA proteins are actually composed of two component proteins, each encoded by a separate gene. HLA-DQ is comprised of DQalpha and DQbeta. There are many possible versions of each of these sub-proteins of HLA-DQ. To be susceptible to Celiac Disease a person has to have HLA-DQ proteins made up of a particular combination of DQalpha and DQbeta protein types. The HLA-DQ proteins with the combinations that can lead to Celiac Disease are called HLA-DQ2 and HLA-DQ8.

HLA-DQ2 and HLA-DQ8 proteins have structures that differ from HLA-DQ proteins made up of other versions of DQalpha and DQbeta. The altered structures of HLA-DQ2

and HLA-DQ8 allow them to bind to gluten. If gluten in the small intestine comes into contact with immune cells displaying HLA-DQ2 or HLA-DQ8 on their surface, the immune system is activated, leading to the symptoms of Celiac Disease.

Within HLA-DQ2 and HLA-DQ8 there are further distinctions of subtypes, some with more or less risk for Celiac Disease. Traditionally, HLA-DQ proteins have been detected using blood tests that look at proteins, not genes. These tests can pick up all subtypes of HLA-DQ proteins associated with Celiac Disease. 23andMe is not able to provide data about all subtypes of HLA-DQ2 and HLA-DQ8. We only report data on one subtype of HLA-DQ2. Of

all the risky HLA-DQ subtypes, this subtype, called HLA-DQ2.5, is most often associated with Celiac Disease.

*******************

LabCorp reports subtypes (at least that's what I read). We'll see.

[JoshB]

HLA-DQA1Marker:rs2187668

Celiac Disease occurs only in people with certain versions of an immune system protein called HLA-DQ. HLA proteins are encoded by a set of genes on chromosome 6. Together the genes are referred to as the "HLA region." Proteins from the HLA family are involved in the immune system's recognition of invaders. They are responsible for presenting bits of foreign proteins to immune cells and triggering the cells to attack.

Functional HLA proteins are actually composed of two component proteins, each encoded by a separate gene. HLA-DQ is comprised of DQalpha and DQbeta. There are many possible versions of each of these sub-proteins of HLA-DQ. To be susceptible to Celiac Disease a person has to have HLA-DQ proteins made up of a particular combination of DQalpha and DQbeta protein types. The HLA-DQ proteins with the combinations that can lead to Celiac Disease are called HLA-DQ2 and HLA-DQ8.

HLA-DQ2 and HLA-DQ8 proteins have structures that differ from HLA-DQ proteins made up of other versions of DQalpha and DQbeta. The altered structures of HLA-DQ2

and HLA-DQ8 allow them to bind to gluten. If gluten in the small intestine comes into contact with immune cells displaying HLA-DQ2 or HLA-DQ8 on their surface, the immune system is activated, leading to the symptoms of Celiac Disease.

Within HLA-DQ2 and HLA-DQ8 there are further distinctions of subtypes, some with more or less risk for Celiac Disease. Traditionally, HLA-DQ proteins have been detected using blood tests that look at proteins, not genes. These tests can pick up all subtypes of HLA-DQ proteins associated with Celiac Disease. 23andMe is not able to provide data about all subtypes of HLA-DQ2 and HLA-DQ8. We only report data on one subtype of HLA-DQ2. Of

all the risky HLA-DQ subtypes, this subtype, called HLA-DQ2.5, is most often associated with Celiac Disease.

*******************

LabCorp reports subtypes (at least that's what I read). We'll see.

That is what 23andme will give you from their interface. The interesting thing, though, is that you can get your raw SNP values and with some work of your own, figure out a lot more. There's a tool called "Promethease" which takes your raw SNP dump and matches it against a database of known risk factors.

[pricklypear1971]

So you've done this, Josh? Does it tell you that you have a specific gene or just that you "are at risk", not naming a gene?

[JoshB]

So you've done this, Josh? Does it tell you that you have a specific gene or just that you "are at risk", not naming a gene?

Yeah, I've done it. It's really interesting. What you get from 23andme is a table of hundreds of thousands of raw SNP values, sometimes an SNP will help you figure how what version of a gene you have. An SNP(single nucleotide polymorphism) is a single "letter" change in a dna strand. Basically they take 10,000 people, fully sequence them and look for places where there are common differences. Then they make a "Chip" that takes your DNA and examines it at all these places. 90% of those changes are meaningless, but sometimes they correlate with something useful. For instance you can find out your DQ values (definitely 2s and 8s, not too sure about the others). You can also use it to find out other HLA information, ancestry data, and all kinds of neat things.

Don't expect too much. DQ values aren't even all that useful, and most genetic info is much less useful than that for determining disease risk.

I would say that what you can find out, if you're willing to do a little work, is about 100X as useful as what I've seen from labcorp and the like.

[IrishHeart]

Enterolab (among others) does Genetic testing and sends you a report via email. Visit their website for info. It's a simple cheek swab. I think they are the least expensive --when we were looking into it in our family. The report is useful if you have tested NEG on celiac blood panels or if you choose not to ingest gluten again for a biospy or if you have all the symptoms and wish to know if there is a genetic predisposition.

OR

You can also ask your doctor to do gene testing through stool samples (if you are not squeamish about such things ) Mine ordered it for me (just to confirm) as I was having other testing for Crohn's and IBD after my celiac DX. It was covered by insurance---with a co-pay.

Either one will indicate the presence of HLA-DQ2 or -DQ8 genes.

Some people develop celiac without the presence of the so-called celiac genes (HLA-DQ2 and DQ8)-but with various sub-types of them. Many members report this on this site.

My doctor told me he has a patient with full-blown celiac and he has neither of those genes. Researchers are working on this very issue. Just goes to show that celiac is much larger than "they" previously thought and that the diagnostic criteria for celiac disease needs to be re-examined.

[pricklypear1971]

Hmmm...I don't know if I'm THAT curious to know my risks for other diseases. Smart money is on knowing, but I find it a bit depressing right now.

[ravenwoodglass]

Some people develop celiac without the presence of the so-called celiac genes (HLA-DQ2 and DQ8)-but with various sub-types of them. Many members report this on this site.

My doctor told me he has a patent with full-blown celiac and he has neither of those genes. Researchers are working on this very issue. Just goes to show that celiac is much larger than "they" previously thought and that the diagnostic criteria for celiac disease needs to be re-examined.

Myself and my children are of this group. I carry a double DQ9 so each child has at least one copy of that gene. Because my DD doesn't have DQ2 or DQ8 her present doctor told her that her positive blood test and biopsy were wrong and she never had and never will have celiac. All her celiac related issues are now considered stress related. There is much still to be learned about the genetics of celiac disease and the presence or absence of those two genes is not diagnostic.

IMHO until they start gene testing ALL diagnosed celiacs the gene panels are of interest but should not be used to firmly rule celiac out.

[pricklypear1971]

Myself and my children are of this group. I carry a double DQ9 so each child has at least one copy of that gene. Because my DD doesn't have DQ2 or DQ8 her present doctor told her that her positive blood test and biopsy were wrong and she never had and never will have celiac. All her celiac related issues are now considered stress related. There is much still to be learned about the genetics of celiac disease and the presence or absence of those two genes is not diagnostic.

IMHO until they start gene testing ALL diagnosed celiacs the gene panels are of interest but should not be used to firmly rule celiac out.

Agreed. But in still going to order it and see.

[ravenwoodglass]

Agreed. But in still going to order it and see.

No reason why you shouldn't. I just fear folks doing the same thing my DD did if they don't have one of those two genes. Gene testing can be a valid part of the diagnostic process and it is interesting to see which genes you do carry.

[IrishHeart]

Because my DD doesn't have DQ2 or DQ8 her present doctor told her that her positive blood test and biopsy were wrong and she never had and never will have celiac. All her celiac related issues are now considered stress related.

OMG, raven.... How on earth does a doctor make such a statement? A positive blood test and biopsy....aren't they considered the "the gold standard" by this archaic medical profession we have in this country? Certainly she knows she has celiac nonetheless, yes?

[frieze]

No reason why you shouldn't. I just fear folks doing the same thing my DD did if they don't have one of those two genes. Gene testing can be a valid part of the diagnostic process and it is interesting to see which genes you do carry.

...and all the documentation of other genes being implicated will be helpful for research....

[ravenwoodglass]

OMG, raven.... How on earth does a doctor make such a statement? A positive blood test and biopsy....aren't they considered the "the gold standard" by this archaic medical profession we have in this country? Certainly she knows she has celiac nonetheless, yes?

Not as far as I know. I am not 'allowed' to bring it up because that is 'nagging'. I worry about her but there is nothing I can do. Since the doctor was an expert at a highly regarded hospital his words bear much more weight than I and I doubt he ever saw her records from her home town GI.

[IrishHeart]

Not as far as I know. I am not 'allowed' to bring it up because that is 'nagging'. I worry about her but there is nothing I can do. Since the doctor was an expert at a highly regarded hospital his words bear much more weight than I and I doubt he ever saw her records from her home town GI.

That's just a shame ...for her to disregard POSITIVE test results based on one guy's opinion. I am sorry to hear this--- as I imagine it is very difficult for you to keep silent. Perhaps, one day, she will see the light. I am going through similar issues with my sister. Total refusal to even consider testing --and clearly, she is as much a celiac as I am. sigh.

As you and I have discussed, had I listened to the "TOP doctors" in my area, I might be dead by now.

[Kay53]

I'm wondering if anyone has done the genetic testing at home and if you had a chance to compare prices and have any wisdom on which ones are best and cheapest. Are you able to use any insurance if you order this for home use? Also, if your Dr. ordered the genetic test for you, I'm wondering if it was covered then, and how much. Mainly because I'll leave my Dr. out of the equation if it's not going to be covered anyway.

Thanks

I had testing done in CO. She told me upfront that it would cost and probably my insurance would not cover it. And she was soooo right. I love everything that she has done for me and finally feeling like a human again, but I just can't afford her anymore and not sure my MD doc will ever be able to fully understand. But the testing was worth it to me cause now I know why I have felt so bad for soooo long

[nora-n]

The dutch gene tested a lot of diagnosed celiacs, and only 92% had the genes!

Open Original Shared Link

here they had DQ2,2

To ravenwodglass: there is even a DQ2,9 or DQ2,3 or whatdoyoucallit, it has 02*in the alpha chain and 0303 in the beta chain

they never tested your alpha chain as far as I know since those tests were not available back then

[IrishHeart]

The dutch gene tested a lot of diagnosed celiacs, and only 92% had the genes!

Open Original Shared Link

here they had DQ2,2

To ravenwodglass: there is even a DQ2,9 or DQ2,3 or whatdoyoucallit, it has 02*in the alpha chain and 0303 in the beta chain

they never tested your alpha chain as far as I know since those tests were not available back then

Thanks so much for this posting, Nora!! I have searched for NEW information on genetic testing and have come up empty.

I have DQ 2,2 and it is considered --granted, now, I am quoting from the lab test results I received--"rarely associated with celiac disease"--about 2%.

Looks as if this number is much larger than previously thought.

We have a long way to go before the researchers figure out just how widespread this disease really is.

[JoshB]

The dutch gene tested a lot of diagnosed celiacs, and only 92% had the genes!

Open Original Shared Link

I think I should point out for anyone stumbling onto this from Google, that this paper doesn't seem to support the conclusions being drawn here. They tested only for DQ2.5 and DQ8. For some reason they did not test for 7.5 or 2.2. The numbers found actually seem to be about what you'd expect, and frankly even if they weren't this is a very poor study and not trustworthy. They've ignored the obvious steps of testing for other known troublesome DQ types, they seem to have no controls, and haven't investigated if some of the people in the study were family members. It's also done over a very small number of people; too small to draw conclusions about DQ types and the probability of celiac disease development.

[IrishHeart]

I think I should point out for anyone stumbling onto this from Google, that this paper doesn't seem to support the conclusions being drawn here. They tested only for DQ2.5 and DQ8. For some reason they did not test for 7.5 or 2.2. The numbers found actually seem to be about what you'd expect, and frankly even if they weren't this is a very poor study and not trustworthy. They've ignored the obvious steps of testing for other known troublesome DQ types, they seem to have no controls, and haven't investigated if some of the people in the study were family members. It's also done over a very small number of people; too small to draw conclusions about DQ types and the probability of celiac disease development.

Actually, I believe the study supports what we are discussing.....if you read it carefully, the conclusion of the study is...

"Using HLA DQ2.5 or DQ8 negativity to exclude celiac disease is unreliable as a relatively high proportion (8.3%) of the celiac disease patients does not carry this heterodimer."

Which means--that in this study of DIAGNOSED CELIACS--a large number of people carry genes OTHER than the proposed "celiac genes" (DQ2 and DQ8) and the absence of those two genetic markers does not negate the possibility of celiac disease.

If that small number of celiacs includes people with genes OTHER THAN the ones recognized as predisposing to celiac disease, then the number may exponentially be larger in the entire celiac population. Many on this site can tell you that they have diagnosed celiac and do NOT carry either the DQ2.5 and DQ8 gene.

[JoshB]

I don't dispute that a test for DQ2.5 and DQ8 is ineffective. But the suggestion I'm getting from this discussion is that genetic testing itself is ineffective as a screening tool. That, I would say, is not supported by the linked paper. The paper proposes a straw-man so that it can have surprising and "controversial" results.

The problem with this is, that I don't think anyone would seriously advocate that the test they propose should be an effective screening tool. It's well known that DQ2.2 and DQ7.5 are also susceptible, so if you exclude them then of course you have an ineffective test.

[nora-n]

DQ2,2 plus DQ7,5 actually register in gene tests as DQ2,5 since it is DQ2,5 in trans.

(but probably Enterolab testing will only give the DQ2,2 result with DQ2,5 in trans since they send their tests to the American Red Cross and only order the beta chain to conserve costs)

[IrishHeart]

The study was not conducted to determine what other genes are involved in celiac disease. That was not the purpose of the study.

The study was to show that some diagnosed celiac patients do not have the "alleged celiac genes" of DQ2 and DQ8. That's all!

They did the study, gave the stats and drew a reasonable conclusion--that 8.3% do not have these genes.

There is nothing Faulty about the study or the conclusion.

Genetic testing is not a diagnostic tool IN and of itself, no. It 's primary purpose USED TO BE to exclude diagnosis if the patient had symptoms suggestive of celiac but tested negative on blood and biopsy. If they did not have DQ2 or DQ8 genetic markers, they were told they did not have celiac. We now know this is WRONG as many others --without DQ2 and DQ8 do indeed have celiac disease.

To further muddy the waters, many people carry HLA-DQ2 and HLA-DQ8 genes and never develop celiac.

Genetic testing, for many people, is used solely to help family members understand the risk of inheriting the disease.

....that's it, I'm done

[JoshB]

Nora, you may be right that they would pick up 7.5 as 2.5; I don't know enough to say for sure, but they specifically indicate that they were not testing for 2.2, and that all the "left-overs" were found to be 2.2. So again, this is exactly the result that previous studies would have us expect. This result should not be surprising or inflammatory, but it's presented in such a way as to come across like that.

Irish, I agree that they were not claiming to test more than 2.5 and 8, but they lead you to try to draw the conclusion that you just explicitly drew: that "Genetic testing is not a diagnostic tool IN and of itself, no. It's primary purpose USED TO BE to exclude diagnosis if the patient had symptoms suggestive of celiac."

Again, I have to say that genetic screening does seem to be very useful in excluding celiac disease. The study could certainly be used to say that screening limited to only DQ2.5 and DQ8 is not useful, but I don't think that anyone should be or are using such screening to begin with.