Dna Test Result Interpretation

[parker]

I have results back for the HLA ABC Typing test (DNA test) for Celiac Disease for my son. After several days of trying, I haven't been able to get my physician to interpret the results. If anyone knows how to do this, I'd appreciate a quick "unscientific" opinion. I'll eventually get the official physicians opinion, but I'm quite impatient at this point.

Here are the details:

Alleles Detected: Serological equivalents:

HLA A*02 Antigen 1: A2

HLA A*03 Antigen 2: A3

HLA B*18 Antigen 1: B18

HLA B*44 Antigen 2: B44

HLA Cw*03 Antigen 1: Cw9

HLA Cw*07 Antigen 2: Cw7

Some internet searching led me to believe that the Cw7 could be a marker, but I didn't know if you needed markers on A and B as well to be considered positive. I think the A and B part are negative.

Please chime in if you know something about this!

Thanks,

Parker

[parker]

After doing more research, I realized the test that was done for my son probably used a more recent nomenclature than what is described in the enterolab tests. Hopefully that will help in targeting appropriate resources for a proper interpretation. I'll copy a little explanation of the enterolab test below, followed by my son's test resutls. Please let me know if you have any suggestions on what his test result mean!

Thanks, Parker

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Explanation of the enterolab tests:

Why are gene results so complicated, and which genes predispose to gluten sensitivity/celiac sprue?

Gene tests for gluten sensitivity, and other immune reactions are HLA (human leukocyte antigen), specifically HLA-DQ, and even more specifically, HLA-DQB1. The nomenclature for reporting HLA gene results has evolved over the last two decades as technology has advanced. Even though the latest technology (and the one we employ at EnteroLab for gene testing) involves sophisticated molecular analysis of the DNA itself, the commonly used terminology for these genes in the celiac literature (lay and medical) reflects past, less specific, blood cell-based (serologic) antigenic methodology. Thus, we report this older "serologic" type (represented by the numbers 1-4, e.g., DQ1, DQ2, DQ3, or DQ4), in addition to the integeric subtypes of these oldest integeric types (DQ5 or DQ6 as subtypes of DQ1; and DQ7, DQ8, and DQ9 as subtypes of DQ3). The molecular nomenclature employs 4 or more integers accounting together for a molecular allele indicated by the formula 0yxx, where y is 2 for DQ2, 3 for any subtype of DQ3, 4 for DQ4, 5 for DQ5, or 6 for DQ6. The x's (which commonly are indicated by 2 more numbers but can be subtyped further with more sophisticated DNA employed methods) are other numbers indicating the more specific sub-subtypes of DQ2, DQ3 (beyond 7, 8, and 9), DQ4, DQ5, and DQ6. It should be noted that although the older serologic nomenclature is less specific in the sense of defining fewer different types, in some ways it is the best expression of these genes because it is the protein structure on the cells (as determined by the serologic typing) that determines the gene's biologic action such that genes with the same serologic type function biologically almost identically. Thus, HLA-DQ3 subtype 8 (one of the main celiac genes) acts almost identically in the body as HLA-DQ3 subtype 7, 9, or other DQ3 sub-subtypes. Having said all this, it should be reiterated that gluten sensitivity underlies the development of celiac sprue. In this regard, it seems that in having DQ2 or DQ3 subtype 8 (or simply DQ8) are the two main HLA-DQ genes that account for the villous atrophy accompanying gluten sensitivity (in America, 90% of celiacs have DQ2 [a more Northern European Caucasian gene], and 9% have DQ8 [a more southern European/Mediterranean Caucasian gene], with only 1% or less usually having DQ1 or DQ3). However, it seems for gluten sensitivity to result in celiac sprue (i.e., result in villous atrophy of small intestine), it requires at least 2 other genes also. Thus, not everyone with DQ2 or DQ8 get the villous atrophy of celiac disease. However, my hypothesis is that everyone with these genes will present gluten to the immune system for reaction, i.e., will be gluten sensitive. My and other published research has shown that DQ1 and DQ3 also predispose to gluten sensitivity, and certain gluten-related diseases (microscopic colitis for DQ1,3 in my research and gluten ataxia for DQ1 by another researcher). And according to my more recent research, when DQ1,1 or DQ3,3 are present together, the reactions are even stronger than having one of these genes alone (like DQ2,2, DQ2,8, or DQ8,8 can portend a more severe form of celiac disease).

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Results from the genetic Celiac test my son received:

I have results back for the HLA ABC Typing test (DNA test) or Celiac Disease for my son. After several days of trying, I haven't been able to get my physician to interpret the results. If anyone knows how to do this, I'd appreciate a quick "unscientific" opinion. I'll eventually get the official physicians opinion, but I'm quite impatient at this point.

Here are the details:

Alleles Detected: Serological equivalents:

HLA A*02 Antigen 1: A2

HLA A*03 Antigen 2: A3

HLA B*18 Antigen 1: B18

HLA B*44 Antigen 2: B44

HLA Cw*03 Antigen 1: Cw9

HLA Cw*07 Antigen 2: Cw7

Some internet searching led me to believe that the Cw7 could be a marker, but I didn't know if you needed markers on A and B as well to be considered positive. I think the A and B part are negative.

Please chime in if you know something about this!

Thanks,

Parker

[Jeagbenne]

I'm not an expert by any means, but I do have a biology degree so I somewhat understand genetics. After doing some research I believe that I can sort of help you.

HLA stands for Human Leukocyte antigen which is a protein called an antigen. An antigen is something that triggers your immune system, it can be something your body makes itself or something introduced to your body from the environment. So, genes make proteins. Everyone's genes make different proteins. HLA is a protein that your body makes that can trigger an autoimmune response. The way a lot of tests check for genes is to actually look for the proteins that those genes make. So, if you have certain HLA's in your blood, then you have the genes that make them. I don't believe that you have the celiac gene, since all the reading I've done indicates that the HLA that causes celiac is in the D class. I'm not a doctor, however and all this medical science stuff is still in it's infancy. Some scientist and doctors still don't agree what genes or proteins cause what diseases, and we still have a lot to discover. One of the things about these tests that is so maddening is that you could seemingly have a disease but they can't detect the gene for it, or you have the gene for something and never get the disease!

Hopefully your doctor will call you back with more expert advice. In the mean time, if the gluten free diet makes you and your son feel better, stick to it. If it isn't broken, don't fix it!

JGB

[2Boys4Me]

Open Original Shared Link

That's a link to the only website I've ever found mentioning HLA-B and celiac disease. I have HLA-B8 which is mentioned on the site and also HLA-B44 (which your son has). I know this only because about 15 years ago I signed up to be a bone marrow donor, and they did HLA-typing and they notified me of 3 HLA types. I think the other one was HLA-A9. I don't have my blood donor card handy. Oddly enough, I do not have Celiac, although I've had several surgeries and plenty of stress in my time, but I guess not enough to act as a "trigger". We don't know anyone else's HLA types in my family.

Not much help to you, but there you have it.

[parker]

I think my faxed results may have been off on one factor, as it was not printed very clearly. I'm guessing Cw*03 should really be Cw09, based on the fact that Cw9 was printed very clearly. Corrected version is:

Alleles Detected: Serological equivalents:

HLA A*02 Antigen 1: A2

HLA A*03 Antigen 2: A3

HLA B*18 Antigen 1: B18

HLA B*44 Antigen 2: B44

HLA Cw*09 Antigen 1: Cw9

HLA Cw*07 Antigen 2: Cw7

[parker]

After doing a little more research and reading this:

"HLA molecules exist in two classes. HLA-A, HLA-B and HLA-C molecules make up the class I molecules and HLA-DR, HLA-DQ and HLA-DP molecules make up the class II molecules."

Given that the test result only listed Type I HLA, I'm wondering if the test even checked for the class II molecules. i.e., could the results be either Class I or Class II, or should they include both Class I and Class II?

Or, does it mean he simply doesn't have the Celiac marker Class II genes?

Still waiting on my doc to get back to me (called again today and "no word yet"), and I'm off for vacation in a couple of days. I sure would like to get this resolved before we leave! (we'll stay gluten-free no matter what, I just hate not understanding the test result)

Parker

[ms-sillyak-screwed]

Are you speaking about DNA tests to see if someone has celiac disease or prone to get it?

I was hoping there is a DNA test for celiac disease. You see I had a group of doctors and a major hospital mess up a celiac disease profile on my dear auntie, that was on a feeding tube, they were pumping her full of gluten and dairy. I fought with them day and night to change her diet. The result was she died. And they botched the celiac disease profile blood work before she was moved to hospice. Open Original Shared Link. What a nightmare! I have some of her DNA and I am still searching for answers to if it is what killed her or the docs misstreatment of her needs.

So my question is there a DNA test for celiac disease?

[Rachel--24]

So my question is there a DNA test for celiac disease?

There are specific genes that can predispose you to getting Celiac (DQ2 & DQ8) but having one of these genes does not prove Celiac. Nearly half the population has one of these genes but not everyone has Celiac.

[parker]

I now believe my son's results reflect the wrong test that was ordered-- it was a more general HLA typing, or at least an outdated test. One of the more well-known labs had this to say about the results:

"Thank you for your correspondence. I have consulted with Dr. ____ on these HLA results, and he has informed me that the tests that were run are somewhat outdated in trying to confirm a predisposition to Celiac Disease. However, it seems that lacking the A1 and B8 genes could indicate that there may be no predisposition to Celiac. This type of gene testing is called linkage disequilibrium, and it is not usually used for this type of testing anymore. Our gene test will give you the exact genes located on the DQB1 location of the DNA strand and we will tell you if they are Celiac, gluten sensitive, or neither. I hope this information has been helpful. Please let me know if I can assist you further. Sincerely, _______"

In any case, I'm going to do the cheek swipe test described above, which seems like a more specific test, with more clear cut results.

I also understand (please correct me if I'm wrong!) that this type of test in only conclusive if it is negative.

Thanks for all the useful information!

Parker

ms_sillyak_screwed:

"So my question is there a DNA test for celiac disease?"

Yes, but it is only conclusive if it is negative (meaning you don't have the genes that predispose you to the disease). If you do have the genes (positive result), you may or may not get celiac disease. i.e., if you have the genes, the test does not show that you have the disease.

ms_sillyak_screwed,

I believe the genetic test described here is one of the better tests, and it's not particularly expensive:

Open Original Shared Link

[Rachel--24]

There are a small percentage of Celiacs who do not have either of the main genes (DQ2 and DQ8). Not having either of these genes greatly reduces your chances of developing Celiac but a negative gene test cannot rule out Celiac with 100% certainty. At this time they have not yet determined every gene involved with Celiac.

[parker]

There are a small percentage of Celiacs who do not have either of the main genes (DQ2 and DQ8). Not having either of these genes greatly reduces your chances of developing Celiac but a negative gene test cannot rule out Celiac with 100% certainty. At this time they have not yet determined every gene involved with Celiac.

Do you happen to know what % of people who DO have Celiac do NOT have the main genes (DQ2 and DQ8)? Until we find out what my son's status is, it doesn't matter for our situation, but if you happen to know, that would be a useful data point for understanding the predisposition for the disease.

Thanks!