Interpreting Your Celiac Genetic Results

[Ninja]

This seems to come up a fair amount, thus I thought it might be helpful to have a collection of relevant information all in one spot. [if you are only looking to interpret your results, skip down to the asterisks.] 

 

Per current knowledge, if you do not possess any of the celiac genes you are not considered to be at risk for developing the disease at any point in your life. It is for this reason that doctors have begun testing for the genes more and more in situations where the diagnosis is unclear, or to establish risk in family members of persons with the disease. However, there have been rare cases where people have been found to be suffering from celiac disease despite not having the genetics to support the diagnosis. And if that is not confusing enough, the University of Chicago Celiac Disease center acknowledges that it is not impossible to have Dermatitis Herpetiformis (DH - the celiac rash) without the celiac genes, as well:

 

"Is it possible to have dermatitis herpetiformis (DH) without having the genes for celiac disease?

It's extremely unlikely to have dermatitis herpetiformis (DH) without the genes for celiac disease, but not impossible. (http://www.cureceliacdisease.org/archives/tag/dermatitis-herpetiformis/page/2)

 

So, doctor's frequently are using genetic tests as a means to rule-out celiac disease. There is one main issue with doing this: the comprehensiveness of testing is widely variable! Some physicians test for all of the celiac-related genes, while others only look for one variation.

 

Essentially, if you do not have the celiac genes but have reason to suspect you are suffering from celiac disease, pursue further testing (via blood and/or endoscopy) prior to going gluten free.

 

***To the nitty gritty... 

 

More often than not (especially if you ordered the tests through your doctor), you'll end up with a piece of paper with lots of numbers and the words present or absent after them. What does it all mean? Briefly,

 

HLA-DQ2

 

HLA-DQA1 *0501 + HLA-DQB1 *0201 = HLA-DQ2.5. (A1 and B1 simply refer to different parts. They are alternatively referred to as the alpha and beta portions) This is the most common haplotype found in celiacs, although it is also very prevalent in non-celiacs as well: up to 30% of the US population (higher in Europe) might have the A1 and/or the B1 portion of this haplotype! It is thought to confer the highest risk, especially when the individual is homozygous (possesses two copies).

 

HLA-DQA1 *0201 + HLA-DQB1 *0202 = HLA-DQ2.2. This haplotype occurs in lower frequencies across the world and is also less common in celiacs. It is thought to confer a potentially 'lower disease risk'. It is important to note that low risk does not equal no risk: this haplotype can mediate celiac disease by itself. Sometimes the A1 or B1 portion of DQ2.2 combines with the A1 or B1 portion of DQ2.5 which confers a marginally higher risk than DQ2.2 alone.

 

HLA-DQA1 *0302 + HLA-DQB1 *0202 = HLA-DQ2.3. As far as I know, DQ2.3 is very similar to DQ2.2. The tests do not often differentiate between the two. 

 

As mentioned above, HLA-DQ2.5 and HLA-DQ2.2 (their alpha and beta portions) may combine with each other in any number of amalgamations, or they may independently combine with other celiac genes (DQ8, DQ7.5), or genes unrelated to celiac disease (DQ5, DQ6,...).

 

HLA-DQ8

 

HLA-DQA1 *0301 OR HLA-DQA1 *0302 + HLA *0302 = HLA-DQ8.1 DQ8 is a less frequent variation worldwide, and thus it is also occurs in smaller numbers within the celiac population. 96+% of celiac's have some form of DQ2 or DQ8.

 

Just like DQ2.5 and DQ2.2 may union with other celiac gene variations, DQ8 can do the same thing.

 

HLA-DQ7

 

Some celiac genetic tests report on DQ7 and others don't. If they do, it is almost always the alpha portion of DQ7.5:

 

HLA-DQA1 *0505. This is part of DQ7.5 and may combine with HLA-DQB1 *0202 (2.2) to raise the risk of celiac in a similar way as HLA-DQ2.5 does. Or, it may combine with HLA-DQB1 *0201 (2.5), which also raises the risk [marginally]. DQ7 can be involved in celiac disease separate from DQ2 as well, but the relationship is not quite as well known as in DQ2 or DQ8.

 

In short:

 

If you have any of the variations under the DQ2 or DQ8 headings, you have a celiac gene. This, however, does not mean you have or will develop the disease. Up to 40% of the US population possesses a celiac gene, but only 1% will go on to develop the disease. Listed below are a few things that will further raise your likelihood [non-comprehensive]:

• Having an immediate family member with the disease.
• Having Type 1 Diabetes.
• Having autoimmune thyroid disease.
• Having a different autoimmune disease, yourself.

Also: a genetic test is not fully comprehensive unless and until it includes all of the alpha and beta variations of DQ2 and DQ8 (listed under their constituent headings above). I am hesitant to include DQ7 in the former statement as I feel there is still more research to be done to further elucidate its involvement with celiac disease. If your genetic results reveal that certain celiac genes are absent, but not all of the variations were tested, you can conclude that your risk of celiac is lower (because it is less likely you will have the more uncommon gene variations), but not non-existant. Gene testing can be a very helpful tool, but rarely the be-all and end-all.

 

I so hope this was helpful to read through! Thanks and best wishes,

Ninja 

 

A few "extras":

 

For those interested: HLA = Human Leukocyte Antigen. HLA is found on a portion of the Major Histocompatibility Complex (MHC) located on chromosome 6. The MHC is frequently discussed/implicated in autoimmune diseases because it houses a large quantity of genes integral to the functioning of the immune system. DQ is a receptor type protein. Roughly, DQ2 and DQ8 can produce a specific kind of protein that, when 'turned on', may begin binding to gliadin (gluten). This bound protein is what the body reacts to, therefore resulting in the autoimmune response characteristic of celiac disease.

 

The wikipedia page has a nice table which lists all of the DQ types – very helpful for interpretation of non-celiac related genes: http://en.wikipedia.org/wiki/HLA-DQ

 

More explanation of the role of DQ7 in celiac: http://celiacdisease.about.com/od/celiacdiseaseglossarygl/g/Hla-Dq7.htm

 

DQ9 has been associated with celiac in asian populations. I am not sure if the studies have been replicated as of yet or where they are in their research on this: http://celiacdisease.about.com/od/celiacdiseaseglossarygl/g/Hla-Dq9.htm

[cyclinglady]

Thanks!

[nvsmom]

You have a great grasp on all that. Thanks for the summary.

[SMRI]

A couple questions--hopefully someone knows the answers..my gene testing for DQ alpha  05:01,05,  for DQ beta 02:01,02:01 Serologic Equivalent: 2,2, does this mean I have two pairs of DQ2 and would have gotten one copy from each parent?  Then, my daughter's tests came back with her DQ alpha 05:01,05 and her DQ beta at 02:01,03 with Serologic Equivalent: 2,7 .  Does that mean that she has DQ7 and would have gotten the 7 from her Dad and perhaps we should have him tested????

[Beckyhux]

Hi, I just read you post, do you think you cold look at a post I just made today in the test section about the results I got for my son? I am very confused! The post is labeled genetic testing by beckyhux for full description.

 

He is positive for DQB1 0201 OR DQB1 0202 it says.  Are those 2 the same thing? Is it indicating one or the other is positive? I don't know why they would list both with "or" and not specify.  Does the beta side of DQ2 get further broken down to 2 parts?

 

Thanks if you have any insight!!

[nora-n]

Beckyhux, the question on 0201 or 0202 just means they tested with a method that does not discriminate between them. Instead they test if 05* is present in the alpha chain.

[CeliacDaniel]

On 5/3/2014 at 1:47 PM, Ninja said:

This seems to come up a fair amount, thus I thought it might be helpful to have a collection of relevant information all in one spot. [if you are only looking to interpret your results, skip down to the asterisks.] 

 

Per current knowledge, if you do not possess any of the celiac genes you are not considered to be at risk for developing the disease at any point in your life. It is for this reason that doctors have begun testing for the genes more and more in situations where the diagnosis is unclear, or to establish risk in family members of persons with the disease. However, there have been rare cases where people have been found to be suffering from celiac disease despite not having the genetics to support the diagnosis. And if that is not confusing enough, the University of Chicago Celiac Disease center acknowledges that it is not impossible to have Dermatitis Herpetiformis (DH - the celiac rash) without the celiac genes, as well:

 

"Is it possible to have dermatitis herpetiformis (DH) without having the genes for celiac disease?

It's extremely unlikely to have dermatitis herpetiformis (DH) without the genes for celiac disease, but not impossible. (Open Original Shared Link

 

So, doctor's frequently are using genetic tests as a means to rule-out celiac disease. There is one main issue with doing this: the comprehensiveness of testing is widely variable! Some physicians test for all of the celiac-related genes, while others only look for one variation.

 

Essentially, if you do not have the celiac genes but have reason to suspect you are suffering from celiac disease, pursue further testing (via blood and/or endoscopy) prior to going gluten free.

 

***To the nitty gritty... 

 

More often than not (especially if you ordered the tests through your doctor), you'll end up with a piece of paper with lots of numbers and the words present or absent after them. What does it all mean? Briefly,

 

HLA-DQ2

 

HLA-DQA1 *0501 + HLA-DQB1 *0201 = HLA-DQ2.5. (A1 and B1 simply refer to different parts. They are alternatively referred to as the alpha and beta portions) This is the most common haplotype found in celiacs, although it is also very prevalent in non-celiacs as well: up to 30% of the US population (higher in Europe) might have the A1 and/or the B1 portion of this haplotype! It is thought to confer the highest risk, especially when the individual is homozygous (possesses two copies).

 

HLA-DQA1 *0201 + HLA-DQB1 *0202 = HLA-DQ2.2. This haplotype occurs in lower frequencies across the world and is also less common in celiacs. It is thought to confer a potentially 'lower disease risk'. It is important to note that low risk does not equal no risk: this haplotype can mediate celiac disease by itself. Sometimes the A1 or B1 portion of DQ2.2 combines with the A1 or B1 portion of DQ2.5 which confers a marginally higher risk than DQ2.2 alone.

 

HLA-DQA1 *0302 + HLA-DQB1 *0202 = HLA-DQ2.3. As far as I know, DQ2.3 is very similar to DQ2.2. The tests do not often differentiate between the two. 

 

As mentioned above, HLA-DQ2.5 and HLA-DQ2.2 (their alpha and beta portions) may combine with each other in any number of amalgamations, or they may independently combine with other celiac genes (DQ8, DQ7.5), or genes unrelated to celiac disease (DQ5, DQ6,...).

 

HLA-DQ8

 

HLA-DQA1 *0301 OR HLA-DQA1 *0302 + HLA *0302 = HLA-DQ8.1 DQ8 is a less frequent variation worldwide, and thus it is also occurs in smaller numbers within the celiac population. 96+% of celiac's have some form of DQ2 or DQ8.

 

Just like DQ2.5 and DQ2.2 may union with other celiac gene variations, DQ8 can do the same thing.

 

HLA-DQ7

 

Some celiac genetic tests report on DQ7 and others don't. If they do, it is almost always the alpha portion of DQ7.5:

 

HLA-DQA1 *0505. This is part of DQ7.5 and may combine with HLA-DQB1 *0202 (2.2) to raise the risk of celiac in a similar way as HLA-DQ2.5 does. Or, it may combine with HLA-DQB1 *0201 (2.5), which also raises the risk [marginally]. DQ7 can be involved in celiac disease separate from DQ2 as well, but the relationship is not quite as well known as in DQ2 or DQ8.

 

In short:

 

If you have any of the variations under the DQ2 or DQ8 headings, you have a celiac gene. This, however, does not mean you have or will develop the disease. Up to 40% of the US population possesses a celiac gene, but only 1% will go on to develop the disease. Listed below are a few things that will further raise your likelihood [non-comprehensive]:

• Having an immediate family member with the disease.
• Having Type 1 Diabetes.
• Having autoimmune thyroid disease.
• Having a different autoimmune disease, yourself.

Also: a genetic test is not fully comprehensive unless and until it includes all of the alpha and beta variations of DQ2 and DQ8 (listed under their constituent headings above). I am hesitant to include DQ7 in the former statement as I feel there is still more research to be done to further elucidate its involvement with celiac disease. If your genetic results reveal that certain celiac genes are absent, but not all of the variations were tested, you can conclude that your risk of celiac is lower (because it is less likely you will have the more uncommon gene variations), but not non-existant. Gene testing can be a very helpful tool, but rarely the be-all and end-all.

 

I so hope this was helpful to read through! Thanks and best wishes,

Ninja 

 

A few "extras":

 

For those interested: HLA = Human Leukocyte Antigen. HLA is found on a portion of the Major Histocompatibility Complex (MHC) located on chromosome 6. The MHC is frequently discussed/implicated in autoimmune diseases because it houses a large quantity of genes integral to the functioning of the immune system. DQ is a receptor type protein. Roughly, DQ2 and DQ8 can produce a specific kind of protein that, when 'turned on', may begin binding to gliadin (gluten). This bound protein is what the body reacts to, therefore resulting in the autoimmune response characteristic of celiac disease.

 

The wikipedia page has a nice table which lists all of the DQ types – very helpful for interpretation of non-celiac related genes: Open Original Shared Link

 

More explanation of the role of DQ7 in celiac: Open Original Shared Link

 

DQ9 has been associated with celiac in asian populations. I am not sure if the studies have been replicated as of yet or where they are in their research on this: Open Original Shared Link

I just got brand new testing in and wanted to know if someone could help me on this one.

Misc Ancillary Test 12~QUEST DIAG

TEST NAME        RESULT

Hla-DQ2            NEGATIVE

Hla-DQ8            NEGATIVE

Hla-DQA1*         01

Hla-DQB1*        0202

Here are the notes, but regardless of what it says is there anything else I should be worried about?

The patient does not have the HLA-DQ variants associated with celiac disease. More than 97% of celiac patients carry either HLA-DQ2(DQA1*05/DQB1*02) or HLA-DQ8(DQA1*03/DQB1*0302) or
both. Genetic counseling as needed.
Masamichi Ito, Ph.D.,FACMG Director, Molecular Genetics Typing performed by PCR and hybridization with sequence specific oligonucleotide probes (SSO) using the FDA-cleared LABType(R) SSO Kit.

Test(s) performed at:
QUEST DIAGNOSTICS CHANTILLY

CLIA #49D0221801
HLA-DQA1* = 02
HLA-DQb1* = 0501
Hla-DQB1* reported incorrectly as 0501 by [2870-VA691].
Changed to 0202 on Feb 21, 2018@14:57 by [2870-VA691].