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Genetic Results


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Half full Newbie

Hi all,

I'm a newbie to the forum, thank you already for the valuable information I've read from this web site.

I'm currently in the middle of a nine month gluten free diet, and drawing blood every few months for the antibodies.

My question is about the genetic profiles. I am HLA-DQ2 and HLA-DQ8 negative, but positive for the

HLA DQA1 05 allele. My understanding is that to get celiac with this profile is rare, and that when someone has celiac with half the DQ2 heterodimer it is most often with the Beta subunit, not the alpha (which I have).

Does anyone else have this profile with being positive for only the alpha subunit?

After 4 months of the diet, my TTGA has stayed around 25 (in the past it's been 25-35). My gliaden IGG in the past has been in the 40's, after 1 month it was still in the 40's, and after 4 months it became negative.

The vague GI symptoms I've had have improved since being on the diet. No more foul smelling gas or BM's. I've never had diarrhea.

Thank you.


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lizard00 Enthusiast

https://www.celiac.com/articles/21628/1/Cel...tics/Page1.html

What is this alpha and beta subunit typing and why is it important?

HLA DQ typing consists of two subunits of the DQ molecule, an alpha and beta subunit. So, both DQ types that indicate a risk of celiac disease, DQ2 and DQ8, are made up of two protein subunits designated alpha and beta. They determine the complex letter and number combinations reported. For example, the full DQ2 molecule is typically HLA DQA1*05xx DQB1*02xx. The A1 is the alpha unit and the B1 is the beta subunit.

The beta subunit is the most important component of the DQ molecule, but the alpha subunit has also been shown to carry an increased risk for celiac disease. Unfortunately, since testing for both is more complicated and expensive it is not always done.

Also, some think that since the beta subunit carries most of the risk and the alpha unit only minor risk, testing for only the beta subunit is adequate. Several clinical laboratories have chosen this approach. They only test for, and report on, DQ2 and DQ8 based on beta subunit types, so their results typically look like this: HLA DQB1*02 detected, DQ2 positive, etc. This is the policy of the laboratory at Bonfils, who also does testing for Quest Diagnostics and Enterolab as well as many hospitals. However, the alpha subunit of DQ2 also carries some risk for celiac disease.

What were your results?

Half full Newbie

Thank you for your reply.

I do not have a specific haplotype (?) result. All I have from Prometheus is that HLA DQA1 05 was detected, and that I am DQ2 and DQ8 negative. They state that some celiacs do have half the DQ2 heterodimer.

Your reply confirms my reading in that most half DQ2 celiacs have the beta subunit and that celiacs with the alpha unit only are rare.

I have had two biopsies done (one with a longer scope) and both came up negative. A capsule endoscopy showed some villi that appeared blunted, but they looked more normal the further you went down the small intestine, and a comment on the report said this COULD be an atypical celiac presentation.

Also, the reason I had the celiac antibodies done in the first place was that I had some elevated liver enzymes most likely related to a minocycline induced hepatitis. In the liver doctor's workup she ran the celiac panel. I also have had a chronic inflammation pattern on the serum electrophoresis with IGG level at one point around 4,000, but now down to about 2,400 (still elevated). They also showed small monoclonal spikes, so I was worked up for myeloma, but that has come back negative, thank god.

The liver enzymes have come back to normal, but they were normal before the diet started.

I guess one concern I have is it possible the chronic inflammation I have giving some false positive celiac antibody tests, or is it more likely it's related to celieac disease.

My doctors have so far been kind of stumped and they hope the celiac diagnosis will tie things together.

Mother of Jibril Enthusiast

DQ7.5 is the only "non-celiac" gene with a *05 alpha allele. It's not as common to have celiac disease in the absence of DQ2 and DQ8, but it's definitely possible... especially with DQ7.5.

Here's what Wikipedia has to say about it:

Open Original Shared Link

A lot of people think the effects of celiac disease are limited to the digestive system, but actually it can cause inflammation in any part of your body... liver, skin, joints, etc... Ever since I figured out my problem with gluten, SO many things are making sense. :)

Half full Newbie
DQ7.5 is the only "non-celiac" gene with a *05 alpha allele. It's not as common to have celiac disease in the absence of DQ2 and DQ8, but it's definitely possible... especially with DQ7.5.

Here's what Wikipedia has to say about it:

Open Original Shared Link

A lot of people think the effects of celiac disease are limited to the digestive system, but actually it can cause inflammation in any part of your body... liver, skin, joints, etc... Ever since I figured out my problem with gluten, SO many things are making sense. :)

Thank you for the link about DQ7.5. I have a science background, and it's fascinating for me to read about these genes and their proteins, even though some of the details are hard to grasp.

I'm going to research DQ7.5 celiac to see if there are any particular presentations associated with it. If anyone has any special knowledge, please chime in. Thanks.

nora-n Rookie

Half the gene--it is not extremely rare. I guess many are missed by the standard tests for DQ2 or 8.

Open Original Shared Link

"HLA types in celiac disease patients not carrying the DQA1*05-DQB1*02 (DQ2) heterodimer: results from the European Genetics Cluster on Celiac Disease.

Department of Tissue Typing, Finnish Red Cross Blood Transfusion Service, Helsinki, Finland.

Genetic susceptibility to celiac disease is strongly associated with HLA-DQA1*05-DQB1*02 (DQ2) and HLA-DQA1*03-DQB1*0302 (DQ8). Study of the HLA associations in patients not carrying these heterodimers has been limited by the rarity of such patients. This European collaboration has provided a unique opportunity to study a large series of such patients. From 1008 European coeliacs, 61 were identified who neither carry the DQ2 nor DQ8 heterodimers. Fifty seven of these encoded half of the DQ2 heterodimer. ........"

Here is more on DQ7 (who have the 05 in the alpha chain) Open Original Shared Link

For more explanation on HLA DQ, and a list of the alpha and beta chains, and what they are, go to wikipedia and find the HLA DQ page, and the HLA DR page too. Often in medical literature they use DR instead...like in Open Original Shared Link

By the way, I wonder what a gene test sent to enterolab would show. Probably Dq7. They tell you all the beta chain results, not just positive or negative for Dq2 or 8.

nora

Half full Newbie

Thank you for the great article on haplotypes of celiacs.

Here are some statistics from the 1008 celiacs from Europe.

DQ2 positive 88%

DQ8 only 6%

DQ2 and DQ8 negative 6%

(1/2 DQ2 heterodimer)

no part of DQ2 heterodimer 0.4% (4 out of 1008 celiacs).

Of the 1/2 DQ2 heterodimer celiacs:

Alpha subunit 28%

Beta subunit 72%

The Alphas all have DQ7.5, of these 19% are homozygous (DQ7.5/DQ7.5).

The Betas all have DQ2.2, of these 27% are homozygous (DQ2.2/DQ2.2).

Of the 1/2 DQ2s that are heterozygous, the other haplotypes break down as:

DQ4 9%

DQ5 47%

DQ6 21%

DQ7 5%

DQ9 19%

Of the four celiacs that had no DQ2 or DQ8 association, three had a DQ5 haplotype.

What suprises me about the data, is that a good percentage (28%) of the 1/2 DQ2 celiacs had the alpha subunit. Everything I had read said the Beta unit was much more important, and that the alpha subunit types (which is me) was much rarer than the Beta type.

This data definitely does not say that.

This data is starting to make me dizzy, time to party.

Happy New Year !!


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nora-n Rookie

I see you had access to the article.

There was much involvement with half a celiac gene plus DQ1, I see.

(DQ5 and DQ6 are DQ1)

and three of the non-half DQ2 were DQ5. Wonder what the fourth was, probably Dq6.

So many 2,2.

It is counted as a gluten sensitive gene only, but here they are, celiacs with 2,2 and without the alpha chain of DQ7,5 (=05*)

(about the DQ1: Hadjivassiliou found that 20% of his gluten ataxia patients were DQ1)

nora

Half full Newbie

The 4 celiacs with no part of dq2 heterodimer break down as follows:

DQ5/DQ5

DQ4.4/DQ5.1

DQ4.4/DQ5.1

DQ7.3/DQ9.2

Sorry, no DQ6. But with only 4 samples, I don't know if you can draw any conclusions.

With DQ2.2, it depends what is paired with.

DQ2.2/DQ2.5 can produce the DQ2.5 heterodimer and 50% of the produced isoforms are dq2.5.

DQ2.2/DQ7.5 can produce the DQ2.5 heterodimer and 25% of the produced isoforms are dq2.5.

DQ2.2/DQ2.2 can NOT produce the DQ2.5 heterodimer, but produces 1/2 (Beta subunit) of it.

In the article, there were actually more DQ2.2/DQ5 (14) than DQ2.2/DQ2.2 (11),

and more DQ7.5/DQ5 (6) than DQ7.5/DQ7.5 (3).

So after the DQ2, DQ8, and the 1/2 heterodimer (DQ2.2 and DQ7.5), it appears DQ5 is next in being prevelent.

nora-n Rookie

I see the last one was DQ7 and DQ9.

We have at least one DQ9 here who got very sick prior to figuring out gluten was the problem. (ravenwoodglass) (she would be interested in this thread, I think, as it has an example of a DQ9 celiac)

and some DQ7.

Usually we do not know our alpha chains here, and we sometimes wish we knew it (for example to know wether one is 7,5 or another type of7)

I see from another tread now here that some can be resolved by DR testing.

I see you got your testing done at Prometheus, and that they did not tell you what the actual beta chains were.

Maybe you are DQ7,5 then.

About the DQ7: DQ7, 8 and 9 are subtypes of DQ3 and differ from each other only by a few amino acid positions:

"..........The DQ8 molecule is highly homologous to two other naturally occurring alleles, DQ7 (DQA1*0301/B1*0301) and DQ9 (DQA1*0301/B1*0303). These three alleles share an identical {alpha} chain (DQA1*0301) and have nearly identical

Half full Newbie

I must be DQ7.5, since Prometheus reported I have DQA1 05, half the heterodimer (and DQ2 and DQ8 negative).

From what I can tell the only possibility would be DQA1 05 - DQB1 03, which is DQ7.5.

nora-n Rookie

I figure it is 7,5 too.

Both DR11 and DR13 have 0505 and 0301 according to Open Original Shared Link , and there is a DR8- 0301 too but that one has 0601 in the alpha chain so that excludes you.

The cart on Open Original Shared Link says similar things.

I was only told I was negative. I think I will order a DQB1 test from Enterolab (they send it out, nowadays it is probably to the American red Cross, but they used to use Bonfils before). I am in Europe so the shipping is expensive and complicated and could cost more than the test itself...I phone d the lab (the very lab that the celiac disease researchers Lundin and co. are using to find out wheat my genes actually were, but they said I should contact my doctor and he is not interested. I asked the lab if they actually could tell me, and she muttered something on DR3 (which just means DQ2) so I do not even know what type of test they did, nor if they can find out what is in the beta chain, or even alpha chain. (that way it would be free for me here, it would not cost anything)

nora

  • 2 weeks later...
dadoffiveboys Rookie

What do my results mean? I *JUST* had genetic results from LabCorp which came back DQ8 positive. They didn't report the allele's so I called them up and they told me on the phone I am this:

DQA1*0302, DQB1*0402 -> DQ4 -> DR4/DQ4 gene haplotype

DQA1*0302, DQB1*0302 -> DQ8 celiac gene -> DR4/DQ8 gene haplotype

BTW I am caucasian and the rep said it was rare to have a DQ4 gene....

I also note that the alpha component is the same as DQ2.3 part and I have THREE copies of the 0302 -> does this put me at a higher risk?? Does this have any bearing on my condition? Also, 100% of my children have some form of gluten intolerance or celiac. According to genetics, EVERY one of my children would receive the DQA1*0302 from me.

Also the DQ4 is SUPPOSED to be some sort of protective gene but I have a rare varient apparently that has a same isomer as a DQ2.3 gene? (but is this alpha sequence a susceptibility to celiac?) Also does this 'protective' gene make it so my blood tests and other tests are seronegative. Yet when I eat gluten I get debilitating back pain such that I cannot move or walk.. and I'll never eat it again obviously!

Of a more interesting note, both the DQ8 and DQ4 genes above encode on the DR4 haplotype and give a double susceptibility to arthritis and diabetes and heart trouble - which I already have! :( (oh yippee).

fedora Enthusiast

dad of five boys,

you only have 2 genes: DQ8 and DQ4

DQA1*0302, DQB1*0402 is the full name of DQ4

DQA1*0302, DQB1*0302 is the full name for DQ8

The 0302 in the alpha part of the DQ4 gene does not confer gluten intolerance.

Just because they numbers are the same, doesn't mean they act the same. You have to look at the entire code and the placing of it.

your children can either get DQ8 or DQ4 from you.

Then they get their other gene from their mom.

I've read the study quoted before. I have the half gene DQ2.2 and DQ5.

I never got blood work or biopsy, so no clue on that, but I had symptoms across many systems in my body that are better now.

ravenwoodglass Mentor
I see the last one was DQ7 and DQ9.

We have at least one DQ9 here who got very sick prior to figuring out gluten was the problem. (ravenwoodglass) (she would be interested in this thread, I think, as it has an example of a DQ9 celiac)

This was an interesting thread. Thanks for posting this info. The genetics of this disease involve so much more than just the DQ2 and DQ8. So many, including my DD, have been told that if those 2 genes are not involved it can't be celiac. I am so thankful I wasn't gene tested during the diagnosis process.

dadoffiveboys Rookie
dad of five boys,

you only have 2 genes: DQ8 and DQ4

DQA1*0302, DQB1*0402 is the full name of DQ4

DQA1*0302, DQB1*0302 is the full name for DQ8

The 0302 in the alpha part of the DQ4 gene does not confer gluten intolerance.

Just because they numbers are the same, doesn't mean they act the same. You have to look at the entire code and the placing of it.

your children can either get DQ8 or DQ4 from you.

Then they get their other gene from their mom.

I've read the study quoted before. I have the half gene DQ2.2 and DQ5.

I never got blood work or biopsy, so no clue on that, but I had symptoms across many systems in my body that are better now.

We also had my middle son tested that was diagnosed with failure to thrive - so it will be interesting to see what HIS gene's are and to see if mom contributed any to it. As a side note, one of my wife's sisters has celiac and her dad had colitis (which we think may have actually been celiac) from a young age... so my wife probably carries a gene as well. I will probably post his results when I get them on here too - they aren't done yet.

nora-n Rookie

Interesting to see that a lab actually tests DR types as well now, so one can both deciper the alpha and beta chains, and that they also provide you with alpha and beta chains.

thefooddoc.com has written about a few patietns who were celiac but lacked the right genes, and he wanted to get the labs to do tha alpha chains as well for that reason.

What worreis me is that we never had anyone report half a celiac gene before, yet there should be many of them according to the study of 1008 cweliacs.

Maybe we will get more reports of half genes now that some labs have started reporting the alpha chains and/or DR types now.

About the DQ4, it is not exclusive to asians. By the way, japanese have a lot of DQ9 and therefore they have some DQ9 celiacs

If you check the DQ types of the 1008 european celiacs, some had DQ4 in combination with other genes.

nora

dadoffiveboys Rookie
Interesting to see that a lab actually tests DR types as well now, so one can both deciper the alpha and beta chains, and that they also provide you with alpha and beta chains.

thefooddoc.com has written about a few patietns who were celiac but lacked the right genes, and he wanted to get the labs to do tha alpha chains as well for that reason.

What worreis me is that we never had anyone report half a celiac gene before, yet there should be many of them according to the study of 1008 cweliacs.

Maybe we will get more reports of half genes now that some labs have started reporting the alpha chains and/or DR types now.

About the DQ4, it is not exclusive to asians. By the way, japanese have a lot of DQ9 and therefore they have some DQ9 celiacs

If you check the DQ types of the 1008 european celiacs, some had DQ4 in combination with other genes.

nora

The lab didn't give me a DR type on the results, they gave me a negative/positive for DQ2/DQ8 only. Labcorp (where I had the test done) doesn't report the alleles on the 'doctor' form - they just said I was DQ8 positive... so I called the HLA testing lab (they provide a contact number) and the woman there said they do the full allele set and was more than happy to provide me my alpha and beta units for both alleles. She said they use very sensitive testing and are fairly accurate. The lab which does this also does HLA tests for organ transplants, DNA testing for paternity, etc. It was the Labcorp HLA lab in Burlington NC that did the testing. The DR subtype I got on the internet comparing my set of alpha/beta to those that are in the DR4 gene type. I COULD be DR8 as well if the testing incorrectly marked my 0302 alpha chains....

However, given I have a very rare cardiac defect at birth (which would be more prevalent in a DR4/DR4 homozygote) I tend to believe the numbers are accurate. My cardiologist said that with the rare cardiac defect at birth, in other patients with similar symptoms, he's been finding undiagnosed celiac after having to undergo valve replacement surgery for aortic stenosis - which is one of the problems associated with the DR4 gene set! (I have a bicuspid aortic valve - which is NOT very common to have this!) Although I don't have diabetes, my uncle DOES and it was helped when he visited by a gluten-free diet (still trying to convince him to go gluten-free). Also my severe muscle pain (in my 30's!) is probably an inflammatory response. My first and only indication I was celiac was an elevated IgA Anti-gliadin which came back "equivocal" and was 2 points under positive (25-50 was equivolcal and I was 48). My wife had similar testing and her IgA was 1. My TTG was also 20 and <=20 was normal and >20 positive.. so I was definitely borderline. Not sure if my DQ4 portion has anything to do with my tests though. Two of my sons had no signs of gluten problems but when I took them off gluten and they got cross-contaminated they had a CLASSIC case of Dermatitis Herpetiformis - broke out to the point of bleeding over their entire buttocks and and welts on the knees and elbows - I find it VERY interesting they only broke out AFTER GOING gluten-free and then being re-contaminated by it! The peditrician was extremely surprised by the quick onset and manifestation of the rash and even said "she's never seen anything like that before..!"

nora-n Rookie

Ah I see they did not give you the DR resutls (but there was a recent posting where someone's doctor ordered DR instead of DQ and interesting things came up)

Very interesting information.

I am sure there are lots of people who would like to or need to know their alpha chains too, and the beta chains.

About the DH rash they got after getting glutened after going gluten free, the reason is the fresly activated T cells:

Open Original Shared Link and some groups are doing trials with small patient selections in order to investigate if they can use these freshly activated T cells to diagnose celiacs. There was something like that going on here where I live. You can find more on pubmed.

About diabetics, and gluten, Alba Therapuetics, wo are doing clinical trials for the new medicine, the zonulin antagonist, also researches zonulin and diabetes. Should be on their website (google it)

Here is a recent thread where we ended up on insulin and gluten and zonulin :

https://www.celiac.com/gluten-free/index.php?showtopic=54390

and search for zonulin on pubmed.com

and the thread about DR:

https://www.celiac.com/gluten-free/index.php?showtopic=53996

nora

dadoffiveboys Rookie

Out of interest sake - I got my son's genetic results.

Sure enough he inherited my DQ8 (0302) gene and has a DQ5 gene (0501). I guess this proves he's my son ;) LOL. Anyways I heard the DQ5 gene is a 'gluten intolerant' gene - is this true?

Anyway he is doing fine as long as we NEVER EVER feed him gluten (sounds kinda like the gremlins movie... Laugh) We actually don't feed that much milk to any of the kids either (drink organic Soy milk instead) as they seem to get constipated with too many milk products. We stick to natural yogurt and hard cheeses and of course ice cream - i.e. let them get the 'good' stuff.

  • 2 weeks later...
craigiecarter Newbie
About the DH rash they got after getting glutened after going gluten free, the reason is the fresly activated T cells:

Open Original Shared Link and some groups are doing trials with small patient selections in order to investigate if they can use these freshly activated T cells to diagnose celiacs. There was something like that going on here where I live. You can find more on pubmed.

nora

Timely, b/c dd must have had trace gluten exposure last week, and within an hour or so, she had a horrible angry looking rash between her legs and stomach cramps. Of course, if you believe all of the recent media on attention-seeking parents torturing their children, she should still be on gluten because she did not test positive by traditional blood tests.

Two years ago, during a gluten-free elimination period, she was with my mother who, being of the belief that it wasn't a big deal, gave her fried dough and she promptly had diarrhea.

It's frustrating to know that there are so many out there who would benefit from gluten-free living, but don't try because the mainstream medical community dismisses their symptoms and/or results (my dd did have a high IgG, but all of her other blood tests were "normal"). Her TtG was elevated when her stool was tested.

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