Question About Implication Of Genetic Testing

[Flor]

Hi all,

I have celiac disease and have one celiac gene and one gluten sensitive gene (or allele I guess to use the better term).

So I had my son tested (he's seven) and his results are identical to mine, right down to the specific string of numbers for both alleles.

I have two questions:

1. Would you immediately get your son off gluten AS IF he had celiac disease because even if we don't see symptoms we can assume gluten over the long term will lead to inflammation? Does anyone address this issue in the literature or research?

2. Would you interpret these results to mean that my husband and I have one or both of these alleles in common? Since I only contribute one allele, then one of these two that my son has had to come from his dad even if it's the same as mine, right? Partly, I'm trying to figure if my husband needs to be tested too in the potential situation that I contributed the gluten sensitive gene and HE contributed the celiac gene to our son. I don't really understand how this stuff works and I read someone on here mention that Enterolab doesn't give the whole result, that there would be FOUR alleles to report. So is it possible the results they've given us are only the alleles I'VE contributed and we actually each contribute two and not one?

Thanks for any insight you all might have!

[MsCurious]

Hi all,

I have celiac disease and have one celiac gene and one gluten sensitive gene (or allele I guess to use the better term).

So I had my son tested (he's seven) and his results are identical to mine, right down to the specific string of numbers for both alleles.

I have two questions:

1. Would you immediately get your son off gluten AS IF he had celiac disease because even if we don't see symptoms we can assume gluten over the long term will lead to inflammation? Does anyone address this issue in the literature or research?

2. Would you interpret these results to mean that my husband and I have one or both of these alleles in common? Since I only contribute one allele, then one of these two that my son has had to come from his dad even if it's the same as mine, right? Partly, I'm trying to figure if my husband needs to be tested too in the potential situation that I contributed the gluten sensitive gene and HE contributed the celiac gene to our son. I don't really understand how this stuff works and I read someone on here mention that Enterolab doesn't give the whole result, that there would be FOUR alleles to report. So is it possible the results they've given us are only the alleles I'VE contributed and we actually each contribute two and not one?

Thanks for any insight you all might have!

Hi Flor,

I might be able to shed some light on your genetic question but FIRST... I would address the issue of your son and gluten-free diet. First, you didn't say if he was showing any symptoms, and if he is I would DEFINITELY get him tested before going gluten-free. Secondly, I would NOT take him off gluten before having him tested by a physician who is familiar with celiac disease. I'm sure you know that once off gluten, it is very difficult to get an accurate positive test (or set of tests is a better way to look at it).

Most importantly, though... you need to understand that not all people who have the genetic markers get celiac disease, or gluten sensitivity/intolerance. If you take your family entirely gluten-free because its easier, with someone in the house that has Celiac, it won't hurt him.

Now... regarding genetic markers... Each parent passes down one pair of alleles that make up a HLA DQ marker. Generally it works like this:

Mom = HLA-DQA1*05/DQB1*02

Dad = HLA-DQA1*01/DQB1*0302

These are just EXAMPLES of how two genetic markers would look. I don't know what yours or your sons or his fathers look like, but son may have gotten ONE genetic marker (one pair of alleles) from mom that BOTH are associated with celiac, or he may have inherited one allele from each parent that is associated with celiac disease, OR... he may have only inherited one allele from one parent, that is celiac disease related. OR he could have inherited two DQ markers that have both pairs of alleles associated with celiac disease. There are lots of possibilities. The chains are sub-units a and b, so he could have an a and b, or two b's, or two sets of a&b that fall into the pool of people who have the possibility of getting celiac disease. Of that pool only a very small percentage of them will develope celiac disease. So basically genetic testing tells you NOTHING... other than he is excluded from the population likely to develop celiac disease, or he is included in that pool, and may possibly develop celiac disease.

Now that I've totally confused you.... If you post the test results ... it might tell more.

[ravenwoodglass]

Not everyone who has the genes will develop the celiac. If he has no symptoms in growth, behavior or any physical issues then just have him blood tested. If he has any symptoms then take him gluten free after all testing is finished no matter what the results as false negatives in children are even more common than with adults. Celiac can develop at any time in life so if he should become symptomatic later have him tested even if he is fine now.

Yes your husband should be tested and if he has any symptoms he should also do a trial of the diet after testing.

In addition your first degree relatives should also be tested, Mother, Father, Brothers and Sisters. Even if they don't seem to have any symptoms.

[Flor]

Thank you for your responses. It's so helpful to have smart people to talk to who have been down this road!

Our tests were done through Enterolab and I gather for some reason they only report one line of alleles or something? I confess I still don't understand this genetic stuff! I've read the basic stuff online and I remember 9th grade biology but this isn't sticking for some reason.

Anyway, our Enterolab results, my son's and mine, were identical:

HLA-DQB1, Allele 1 0201

HLA-DQB1, Allele 2 0603

Serologic equivalent: HLA-DQ 2, 1 (subtype 2,6)

I gather that "0201" is the celiac allele and the "0603" is the gluten sensitive one.

I don't understand, if we each contribute two alleles, why Enterolab only reports two out of four. How do they choose to leave off half the information? Do Allele 1 and 2 represent contributions from mother and father or not necessarily? I sent them an email to ask this question -- I don't understand if the fact that our results are identical means that my husband and I have at least one of the same alleles or if it doesn't mean that at all.

As to the second issue of blood testing before going gluten free...I guess the puzzle I'm having with that is this: it seems like the boundaries of what is considered "having celiac" versus not "having celiac" may be shifting down the line. New research indicates people can have celiac and be at higher risk for cancers long-term even if they show no villi damage. And if the false negatives in the blood test are possible and are higher for kids, then a negative blood test doesn't really seem to say much. If a positive blood test would lead us for sure to go gluten free, then wouldn't a negative one still likely lead us to go gluten free?

I may be lost in this but my thinking is that if celiac disease is widely underdiagnosed, that it takes years on average to diagnosis, and that 99% of the people who ARE diagnosed have the gene, then wouldn't we be risking long-term inflammation and damage by continuing to feed our son gluten even if he isn't actively symptomatic? So many of the symptoms it seems to me in retrospect are vague and low-grade for years. I mean, is feeding gluten to a child who has the gene so different from say smoking -- ie, taking in a substance that over the long-term has the potential to cause real harm? I'm not arguing FOR this position; I'm more struggling with how to hold this given that we know how underdiagnosed celiac disease is and how much higher the risk for cancer for those who have it and keep eating gluten.

Thank you for the conversation here!

[starrytrekchic]

The thing about basing it off the genetic tests without any symptoms is that ~25-30% of the population has the DQ2 genes, while >1% has celiac disease. Different version of DQ2 have stronger relationships with celiac (as do people with double DQ 2 genes), but in and of itself, the gene isn't enough to give you celiac.

[Flor]

Do you know which DQ2 genes are more strongly associated with celiac or where I might read more about that? I hadn't heard about that.

The whole question of gauging when one is symptomatic is a bit mysterious to me. So here are two examples:

1. My son, seems like maybe his BMs get softer after lots of bread eating. Could be candida or unrelated or a potential symptom? He also seems to be developing some mild pre-asthma type symptoms. I know several people diagnosed celiac in their twenties who were diagnosed with exercise-induced asthma in their teens and they now regard their respiratory symptoms as gluten-related. So are my son's respiratory symptoms potential celiac symptoms? He also gets tired a bit more than you'd think for a healthy young seven year old but his immune system is otherwise strong and any doctor who looks at him would say "this is a healthy kid."

2. My niece, who also has the gene, is 22 and for the last year has been having headaches, nausea, fatigue and depression/anxiety. Would we consider these celiac symptoms? This seems so tricky to me because a ton of what in hindsight looks like early celiac symptoms are things that people go for years without seeing a doctor for.

My situation wasn't that confusing because I was 40 and very sick and completely disabled by my guts by the time I was diagnosed. But my guess is I would never have gotten to that point if I hadn't been eating bread like a fiend for 40 years before that. You know?

I guess part of me wonders if in ten or fifteen or twenty years we'll look back on the 1% of the 33% with the gene having celiac disease and realize that number is totally wrong based on a more subtle understanding of inflammation in the body and the long-term effects of that inflammation and stress.

[cassP]

Flor: ok, im not a doctor or a scientist- so this explanation is gonna sound elementary & amateurish...

but i THINK- for example:

your son has 1 DQ2 & 1 DQ6. if these are "allelles".. i believe we only have 2- 1 from the mom and 1 from the dad. enterolab DOES test for the 2 allelles... but ONLY EITHER the "alpha" or the "beta" part of the allelle (i ThINK that's right).

for example- your son MAY have a DQ2.5 or a DQ2.something else. and Enterolab only tests for that 1st part.

did that make sense??

also u asked which genes are more associated- DQ2 & DQ8 are the "classic" celiac genes... all the other DQ genes are "gluten sensitive"... BUT- we are now finding people with Celiac with DQgenes that are NOT 2 or 8.

hope i am correct and it made sense

[zimmer]

I understand your dilemma.

I have 2 little ones, ages 6 & 4, both negative blood work, no symptoms that are readily apparent. I know they have inherited something from me. So I have had the same question - take them gluten-free in anticipation & prevention, or wait for symptoms, or what to do? With their 2 older sisters and me having gluten issues, it stands to reason that they may too as they get older.

We have done no gene testing. I've considered it, but it's too complicated to be of much use to my simple self. I would forget what it all means about the time that I figured it out, and certainly couldn't explain it to anyone. Like I said before, I know they inherited something from me and possibly from their father.

Result - at home, except for sandwich bread & occasional take-out pizza for the gluten-eaters, we are gluten-free. It's simpler that way, and easier for me to avoid gluten. Plus it won't hurt anyone NOT to eat the stuff.

I don't try to control every little thing they eat away from home. If they start to develop symptoms, then we will adjust. By the time they get older, they will have developed (or at least been modeled) gluten-free eating habits and can make an easier transition if necessary or if simply by choice. I have read enough about wheat/gluten to understand that it's not really something we should be eating anyway, and that is certainly going to become a part of their dietary education.

[Flor]

CassP and Zimmer, thank you for writing!

CassP, I THINK I get what you're saying and the thing about only testing half of each allele sounds like what i read elsewhere, though I don't really understand why or what that's about. And if they give numbers like 0201 and 0202 (those are my niece's results), then what's the missing information?

I just re-read my nieces results (0201 and 0202) and their analysis of her situation is actually worse than mine (0201 and 0603) because they say having both alleles be subtype 2, even though 0202 is not BY ITSELF associated with celiac disease, makes her predisposition to celiac disease higher and her symptoms more likely to be worse.

And obviously having two copies of 0201 would be still worse because then both alleles are celiac associated. At any rate, the combination of these alleles seems significant as well, which then makes me wonder what it means to only report on half the allele. I'm still confused about that.

Zimmer, I like your intuitive approach to all this. It sounds like you've found a way to hold this for your family that works for you. That's exactly what I'm looking for in my own way. Given that we understand that the science is still unfolding and that there's a lot we don't understand about long-term effects of low-grade inflammation on the body, my inclination is to err on the side of safe. There are so many insults out there already -- viral, environmental, emotional stressors -- that we now know can all increase chances of a wide range of chronic diseases. So it seems where we can that reducing the potential insults to the body starting at an early age is a good way to go.

Just one small side example: our son got strep throat a couple of years ago and the scarlet fever rash that sometimes comes with it. I gather if a kid gets the scarlet fever rash, that's some indication that they are vulnerable to auto-immune disorders (like kids who have bad eczema for example). He further developed some signs of PANDAs after the strep (these are auto-immune linked neurological symptoms following strep that usually self-resolve and his did). Now none of this has directly to do with celiac disease, but it starts to paint a picture of a kid who might be prone to auto-immune responses over his lifetime. He also had severe reactions to a couple of vaccines, to the point that we didn't do followup boosters (I mean, even the CDC would have agreed with us on this and his doctor recommended we stop all vaccines until he's 11 and his immune system is more mature). These kinds of "extraneous" details make up a picture to me but it's one that mainstream medicine doesn't yet recognize I don't think.

Anyway, just thinking out loud again...

Thanks so much!

[MsCurious]

I understand your dilemma.

I have 2 little ones, ages 6 & 4, both negative blood work, no symptoms that are readily apparent. I know they have inherited something from me. So I have had the same question - take them gluten-free in anticipation & prevention, or wait for symptoms, or what to do? With their 2 older sisters and me having gluten issues, it stands to reason that they may too as they get older.

We have done no gene testing. I've considered it, but it's too complicated to be of much use to my simple self. I would forget what it all means about the time that I figured it out, and certainly couldn't explain it to anyone. Like I said before, I know they inherited something from me and possibly from their father.

Result - at home, except for sandwich bread & occasional take-out pizza for the gluten-eaters, we are gluten-free. It's simpler that way, and easier for me to avoid gluten. Plus it won't hurt anyone NOT to eat the stuff.

I don't try to control every little thing they eat away from home. If they start to develop symptoms, then we will adjust. By the time they get older, they will have developed (or at least been modeled) gluten-free eating habits and can make an easier transition if necessary or if simply by choice. I have read enough about wheat/gluten to understand that it's not really something we should be eating anyway, and that is certainly going to become a part of their dietary education.

You really don't need to know anything about genetics to gain some peace of mind from having your kids tested. Basically, the two genes associated with Celiac (confirmed... no questions asked) are DQ2 and DQ8. You should have your kids tested for them for one very simple reason. If they do not have either of those genes, the likelyhood of them ever developing celiac disease is pretty minuscule, and you don't have to worry about them in the future. If they do carry either of those genes, you will want to watch for symptoms and have the doctor run serology test on them every so often, to make sure they are not producing antibodies. Its really that simple. IF they don't carry DQ2 or DQ8...no worries, if they DO carry DQ2 or DQ8... keep an eye on them. They only have a very small percent chance of developing celiac disease even if they do carry the a celiac disease gene.

[cassP]

which then makes me wonder what it means to only report on half the allele. I'm still confused about that.

Now none of this has directly to do with celiac disease, but it starts to paint a picture of a kid who might be prone to auto-immune responses over his lifetime. He also had severe reactions to a couple of vaccines, to the point that we didn't do followup boosters (I mean, even the CDC would have agreed with us on this and his doctor recommended we stop all vaccines until he's 11 and his immune system is more mature). These kinds of "extraneous" details make up a picture to me but it's one that mainstream medicine doesn't yet recognize I don't think.

Anyway, just thinking out loud again...

Thanks so much!

i think the reason why Enterolab only tests 1 1/2 of each allelle- is because it's cheaper. i THINK.

i also think (altho i could be wrong ) that if you have 2 copies of the same gene- it COULD make that person even more vulnerable? but im just thinking outloud.

and i dont doubt at all that your kid had all those autoimmune reactions and reactions to vaccines... it seems that those of us with autoimmune genes seem to be more susceptible to other autoimmune diseases... or having HYPER immune reactions to other pathogens or vaccines. it all makes sense to me. a vaccine or the virus itself jars an immune system- and if it's already in OVERDRIVE- then all kinds of things can go awry.

good luck with all the testing.

[ravenwoodglass]

You really don't need to know anything about genetics to gain some peace of mind from having your kids tested. Basically, the two genes associated with Celiac (confirmed... no questions asked) are DQ2 and DQ8. You should have your kids tested for them for one very simple reason. If they do not have either of those genes, the likelyhood of them ever developing celiac disease is pretty minuscule, and you don't have to worry about them in the future. If they do carry either of those genes, you will want to watch for symptoms and have the doctor run serology test on them every so often, to make sure they are not producing antibodies. Its really that simple. IF they don't carry DQ2 or DQ8...no worries, if they DO carry DQ2 or DQ8... keep an eye on them. They only have a very small percent chance of developing celiac disease even if they do carry the a celiac disease gene.

I have to disagree with this. Not all celiacs who are diagnosed have their genes tested and gene testing is in it's infancy. There may be many more genes associated with celiac that we don't know of yet and it can even make a difference depending on where in the world you live as to what is considered a celiac associated gene. The gene testing in my family resulted in disasterous results. My DD was diagnosed by both blood and biopsy and did well on the diet. When she left home for college she was close to a very large hospital and as on the diet she was now feeling fine and it was inconvient she went for gene testing. It was found that she didn't have one of those 2 genes and she was told she would never develop celiac and the blood and biopsy were wrong. That prompted me to get my genes tested, I am a firmly diagnosed celiac, and I don't have them either, but my genes are considered celiac associated in the Middle and Far East. Long story short my DD now considers all her celiac symptoms to be stress related. The last time I saw her she was so thin I was shocked. There is nothing I can do because in her mind the doctors that did the gene testing trump her GI's diagnosis from her teens.

We can never assume that if we don't have those 2 genes that we can relax and figure that we will never develop celiac. To do so could be very costly.

[MsCurious]

I have to disagree with this. Not all celiacs who are diagnosed have their genes tested and gene testing is in it's infancy. There may be many more genes associated with celiac that we don't know of yet and it can even make a difference depending on where in the world you live as to what is considered a celiac associated gene. The gene testing in my family resulted in disasterous results. My DD was diagnosed by both blood and biopsy and did well on the diet. When she left home for college she was close to a very large hospital and as on the diet she was now feeling fine and it was inconvient she went for gene testing. It was found that she didn't have one of those 2 genes and she was told she would never develop celiac and the blood and biopsy were wrong. That prompted me to get my genes tested, I am a firmly diagnosed celiac, and I don't have them either, but my genes are considered celiac associated in the Middle and Far East. Long story short my DD now considers all her celiac symptoms to be stress related. The last time I saw her she was so thin I was shocked. There is nothing I can do because in her mind the doctors that did the gene testing trump her GI's diagnosis from her teens.

We can never assume that if we don't have those 2 genes that we can relax and figure that we will never develop celiac. To do so could be very costly.

Hey Raven, I understand your personal frustration with my comment above, but let me address that so as not to confused you or anyone else. Research doctors will tell you (and Joseph A Murray, head of Celiac Research at Mayo Clinic in Rochester, MN told me this specifically) that genetic testing really has very little value in determining/diagnosing celiac disease. Its value is in the "known" DQ2 and DQ8 genes, and the fact that they can tell you if there is cause for concern or not.

As I stated above, there is a VERY minuscule chance that someone could have celiac disease without those two genes, as you do, but you are a RARE population, a TINY % of all celiacs will not have DQ2 or DQ8. The value in genetic testing is what they DO know and what it can rule out. For the most part nearly 100% of celiac disease patients will have one of those two genes.

I'm not trying to discount you at all! Never say never, and you are living proof of that, but within the Celiac population 99.something % of people will be either DQ2 or DQ8, and the others are rare. They are finding genetics that coincide with "other" gluten sensitivities that are equally as important to attend to as celiac disease... they just haven't identified the genes, or given those specific sensitivites "names" like Celiac Disease. They may not have "names" yet... or "known" genes associated with them... but they will, and they are every bit as valid as DQ2/DQ8 and Celiac Disease.

They are uncovering a plethera of gluten sensitivities, and who knows how they will eventually categorize them. They may call them all Celiac and give them a sub-group name, or they may give each new-found and genetically identifiable gluten sensitivity its own name and category. That remains to be seen. Like you said, this is all in its infancy and they are learning new things every day, thank goodness!

[MsCurious]

CassP and Zimmer, thank you for writing!

CassP, I THINK I get what you're saying and the thing about only testing half of each allele sounds like what i read elsewhere, though I don't really understand why or what that's about. And if they give numbers like 0201 and 0202 (those are my niece's results), then what's the missing information?

I just re-read my nieces results (0201 and 0202) and their analysis of her situation is actually worse than mine (0201 and 0603) because they say having both alleles be subtype 2, even though 0202 is not BY ITSELF associated with celiac disease, makes her predisposition to celiac disease higher and her symptoms more likely to be worse.

And obviously having two copies of 0201 would be still worse because then both alleles are celiac associated. At any rate, the combination of these alleles seems significant as well, which then makes me wonder what it means to only report on half the allele. I'm still confused about that.

Zimmer, I like your intuitive approach to all this. It sounds like you've found a way to hold this for your family that works for you. That's exactly what I'm looking for in my own way. Given that we understand that the science is still unfolding and that there's a lot we don't understand about long-term effects of low-grade inflammation on the body, my inclination is to err on the side of safe. There are so many insults out there already -- viral, environmental, emotional stressors -- that we now know can all increase chances of a wide range of chronic diseases. So it seems where we can that reducing the potential insults to the body starting at an early age is a good way to go.

Just one small side example: our son got strep throat a couple of years ago and the scarlet fever rash that sometimes comes with it. I gather if a kid gets the scarlet fever rash, that's some indication that they are vulnerable to auto-immune disorders (like kids who have bad eczema for example). He further developed some signs of PANDAs after the strep (these are auto-immune linked neurological symptoms following strep that usually self-resolve and his did). Now none of this has directly to do with celiac disease, but it starts to paint a picture of a kid who might be prone to auto-immune responses over his lifetime. He also had severe reactions to a couple of vaccines, to the point that we didn't do followup boosters (I mean, even the CDC would have agreed with us on this and his doctor recommended we stop all vaccines until he's 11 and his immune system is more mature). These kinds of "extraneous" details make up a picture to me but it's one that mainstream medicine doesn't yet recognize I don't think.

Anyway, just thinking out loud again...

Thanks so much!

Hi again Flor,

I think you guys are confusing serotype groups with allele groups and haplotype isoforms. This explanation may help you sort through it a bit better:

"HLA-DQ2 (DQ2) is a serotype group within HLA-DQ (DQ) serotyping system. The serotype is determined by the antibody recognition of β2 subset of DQ β-chains. The β-chain of DQ is encoded by HLA-DQB1 locus and DQ2 are encoded by the HLA-DQB1*02 allele group. This group currently contains 2 common alleles, DQB1*0201 and DQB1*0202. HLA-DQ2 and HLA-DQB1*02 are almost synonymous in meaning. DQ2 β-chains combine with α-chains, encoded by genetically linked HLA-DQA1 alleles, to form the cis-haplotype isoforms. These isoforms, nicknamed DQ2.2 and DQ2.5, are also encoded by the DQA1*0201 and DQA1*0501 genes, respectively."

The cis-haplotype isoforms are genetically linked "alleles that form DQ2.5 and DQ2.2 (meaning two specific HLA-DQA1*XX/DQB1*XXXX alleles that are always genetically linked). There are also trans-haplotype isoforms that are essentially when you get an allele from one parent and an allele from the other parent and TOGETHER those two alleles form the same genetically linked haplotype isoform, as someone else that got both from one parent. That is the difference between cis-haplotype isoforms and trans-haplotype isoforms. Am I confusing you even more?

[MsCurious]

Do you know which DQ2 genes are more strongly associated with celiac or where I might read more about that?

Hey Flor, Here is a tidbit that "sort of" answers your question:

"DQ2 represents the second highest risk factor for coeliac disease, the highest risk is a close family member with disease. Due to its link to coeliac disease, DQ2 has the highest association of any HLA serotype with autoimmune disease, close to 95% of all coeliacs have DQ2, of that 30% have 2 copies of DQ2. Of the DQ2 homozygotes who eat wheat, life long risk is between 20 and 40% for coeliac disease.

The relationship of DQ2 and coeliac disease, however, is complex because there are multiple DQ2 isoforms. The DQ α5β2 (DQ2.5) isoform is strongly associated with celiac disease. This isoform is partially encoded by the DQB1*02 genes in HLA-DQ2 positive individuals. DQB1*0201 is genetically linked to DQA1*0501 forming the DQ2.5 haplotype that encodes both α5 and β2 subunits. The DQ2.5 haplotype confers the single highest genetic risk for disease, however comparable risk can also come from very similar alleles on different haplotypes."

If you want to get really technical and understand the inner workings of the HLA-DQ Serotyping System specifically related to DQ2, a good starting point is here:

Open Original Shared Link Hope this helps with some of your questions and confusion. I know it can be very confusing.

[MsCurious]

Flor: ok, im not a doctor or a scientist- so this explanation is gonna sound elementary & amateurish...

but i THINK- for example:

your son has 1 DQ2 & 1 DQ6. if these are "allelles".. i believe we only have 2- 1 from the mom and 1 from the dad. enterolab DOES test for the 2 allelles... but ONLY EITHER the "alpha" or the "beta" part of the allelle (i ThINK that's right).

for example- your son MAY have a DQ2.5 or a DQ2.something else. and Enterolab only tests for that 1st part.

did that make sense??

also u asked which genes are more associated- DQ2 & DQ8 are the "classic" celiac genes... all the other DQ genes are "gluten sensitive"... BUT- we are now finding people with Celiac with DQgenes that are NOT 2 or 8.

hope i am correct and it made sense

cassP you're so cute! LOL I love reading your posts! And yes, I would agree with your "findings' Hehee... Flor's son appears to have DQ2 and DQ6. Your "verbage" is a little "off" but you got to the root effectively enough. Hehee.. I'm still smiling...

[Jestgar]

There are a number of genes associated with susceptibility to celiac disease: Open Original Shared Link

CELIAC2 on Chromosome 5q31-q33

CELIAC3 on Chromosome 2q33

This locus is associated with variation in the CTLA4 gene (123890).

CELIAC4 on Chromosome 19p13.1

This locus is associated with mutation in the MYO9B gene (602129).

CELIAC5 on Chromosome 15q11-q13

CELIAC6 on Chromosome 4q27

See CELIAC6 (611598) for a celiac disease susceptibility locus on chromosome 4q27 within a linkage disequilibrium (LD) block encompassing the KIAA1109 (611565), TENR (ADAD1), IL2 (147680), and IL21 (605384) genes.

CELIAC7 on Chromosome 1q31

This locus may be associated with variation in the RGS1 gene (600323).

CELIAC8 on Chromosome 2q11-q12

See CELIAC8 (612006) for a celiac disease susceptibility locus on chromosome 2q11-q12 within a linkage disequilibrium block encompassing the IL18RAP (604509) and IL18R1 (604494) genes.

CELIAC9 on Chromosome 3p21

See CELIAC9 (612007) for a celiac disease susceptibility locus on chromosome 3p21 within a linkage disequilibrium block encompassing a cluster of chemokine receptor genes.

CELIAC10 on Chromosome 3q25-q26

See CELIAC10 (612008) for a celiac disease susceptibility locus on chromosome 3q25-q26 within a 70-kD linkage disequilibrium block near the IL12A gene (161560).

CELIAC11 on Chromosome 3q28

See CELIAC11 (612009) for a celiac disease susceptibility locus on chromosome 3q28 within a linkage disequilibrium block near the LPP gene (600700).

CELIAC12 on Chromosome 6q25

See CELIAC12 (612010) for a celiac disease susceptibility locus on chromosome 6q25 within a linkage disequilibrium block encompassing the TAGAP gene (609667).

CELIAC13 on Chromosome 12q24

This locus may be associated with variation in the SH2B3 gene (605093).

To say that only two HLA variants are involved is incorrect.

[cassP]

i think in some ways- im a very smart person.. but i think its obvious i am not going to become a Geneticist

i mean- i can understand all these links & risks & symptoms better than most of my docs- but those dang numbers & letters u guys are posting are hurting my brain

my brain just does fine with only the "subtype" numbers

[MsCurious]

i think in some ways- im a very smart person.. but i think its obvious i am not going to become a Geneticist

i mean- i can understand all these links & risks & symptoms better than most of my docs- but those dang numbers & letters u guys are posting are hurting my brain

my brain just does fine with only the "subtype" numbers

You do great! I just stumble around with it too.

[Flor]

Oh my goodness MsCurious this is all fantastically helpful and you are so deep into it I can barely follow you! I will go read that wikipedia stuff. I really am interested in understanding it.

In both your quoted excerpts here I don't understand what this means: "This isoform is partially encoded by the DQB1*02 genes in HLA-DQ2 positive individuals." I don't know what partially encoded means and I don't get how to read the DQB1*02 string.

Is this saying 1. that people with the 0201 in their beta strand (which my son and I have) will usually also have the 0501 in the alpha strand (and this is info that Enterolab doesn't provide because they only give the beta strand info)? and that 2. therefore people with the 0201 isoform have "the single highest genetic risk" for getting celiac disease?

Thank you thank you for hanging in there with me on this!

I hadn't read anywhere the data about DQ2 homozygotes having lifelong risk of 20-40% for getting celiac so that's really interesting. My son and I are DQ2 homozygotes? That means we have one version (isoform?) of the DQ2 (ie, 0201) allele but not two copies of it?

If I'm understanding that right then it seems like someone like my son who is related to me who DOES have celiac disease and he has the 0201 isoform that that would put him at two higher-risk groups among those who have some kind of genetic predisposition for celiac disease. Does that make sense?

[MsCurious]

Oh my goodness MsCurious this is all fantastically helpful and you are so deep into it I can barely follow you! I will go read that wikipedia stuff. I really am interested in understanding it.

In both your quoted excerpts here I don't understand what this means: "This isoform is partially encoded by the DQB1*02 genes in HLA-DQ2 positive individuals." I don't know what partially encoded means and I don't get how to read the DQB1*02 string.

Is this saying 1. that people with the 0201 in their beta strand (which my son and I have) will usually also have the 0501 in the alpha strand (and this is info that Enterolab doesn't provide because they only give the beta strand info)? and that 2. therefore people with the 0201 isoform have "the single highest genetic risk" for getting celiac disease?

Thank you thank you for hanging in there with me on this!

I hadn't read anywhere the data about DQ2 homozygotes having lifelong risk of 20-40% for getting celiac so that's really interesting. My son and I are DQ2 homozygotes? That means we have one version (isoform?) of the DQ2 (ie, 0201) allele but not two copies of it?

If I'm understanding that right then it seems like someone like my son who is related to me who DOES have celiac disease and he has the 0201 isoform that that would put him at two higher-risk groups among those who have some kind of genetic predisposition for celiac disease. Does that make sense?

I'm must confess I love the science of genetics, and since it hits home with me and my family a little bit, I've been like a sponge studying this topic a bit. I'm no expert by any stretch of the imagination, though. I'm happy to help de-mystify if I can though... because it is rather confusing sometimes.

To simplify things for you.... lets start at the top. You said your son's results were as follows: (please correct me if I'm wrong)

HLA-DQB1, Allele 1 0201

HLA-DQB1, Allele 2 0603

I think you said you had Enterolab (I've heard questionable things about some of their testing... maybe its cutting edge, maybe they're reaching for $$$ ... I don't know, but I think their genetic testing is accurate from what I have heard). Someone posted somewhere that this particular lab doesn't send the alpha findings, but the DQB1 alleles you have there are distinctively genetically linked to specific DQA1 alleles, as follows:

HLA-DQA1*05/DQB1*0201 carries the "nickname" DQ2.5 ... and that is most probably what your son has. I'm not certain, but I believe that those two alleles are always associated together. There is another DQB1 allele that is also associated with this same DQA1*05 marker... don't quote me, because I'm going from memory but its something like DQB1*0202 and those two together make DQ2.2.

DQ2.5 is the second highest risk factor to the possibility of celiac... the first being "a first degree family member having been diagnosed with celiac disease".

This HLA-DQA1*05/DQB1*0201 marker if received in its entirety from one parent is cis-haplotype isoform, while someone who received one allele from each parent (DQA1*05 from one parent and DQB1*0201 from the other parent) has trans-haplotype isoform. (this really doesn't matter other than... with the trans there is less risk for other members of the family to be affected.) The isoforms are the two pairs of alleles that are genetically linked ... as in HLA-DQA1*05/DQB1*0201 <--- this example.

His other genetic marker could likely play out as: HLA-DQA1*01/DBQ1*0603 which I believe translates to DQ6. Don't hold me to that, but those two alleles are genetically linked as well, and that would be a typical pair.

At any rate, your son is DQ2 positive. The other marker (DQ6 from my best guestimation) really doesn't relate to celiac disease as far as I know, and actually carries preventative properties to autoimmune disease, which may protect some people a bit from getting celiac disease even if they have DQ2.5... or at least perhaps prolonging the onset. (This set happens to be the same as me... maybe we're related!)

I hope I haven't confused you more. Let me know if I can boggle your mind some more..lol Its just a fun thing... that I enjoy. ;) Again... I'm no expert... those are just "Dr MsCurious' findings" ... like cassP's.

[MsCurious]

Anyway, our Enterolab results, my son's and mine, were identical:

HLA-DQB1, Allele 1 0201

HLA-DQB1, Allele 2 0603

Serologic equivalent: HLA-DQ 2, 1 (subtype 2,6)

I gather that "0201" is the celiac allele and the "0603" is the gluten sensitive one.

As far as I know DQB1*0603 has no relation to celiac disease, and in fact may have preventitive properties to autoimmune diseases... that's GOOD news!

Curious, by the way... do you happen to be of Dutch or German ancestry? And is there a lot of asthma, allergies, hayfever or eczema in your family history? No need to answer if you don't want to, just curious for a couple of different reasons, one being... it appears that I have the same genetic markers as you and your son. (I'm assuming the Irish... am I right?)

[Roda]

Wow, I'm confused just reading this topic. I never had the genetic testing and am firmly diagnosed by blood and biopsy. I'm not getting my children gene tested either. I'm good with it.

[sa1937]

I've never had gene testing either and this topic also confuses me. I do know that I have celiac and my adult daughter has it, too. Since gene testing is not diagnostic, I've never even given it another thought.

[ravenwoodglass]

I've never had gene testing either and this topic also confuses me. I do know that I have celiac and my adult daughter has it, too. Since gene testing is not diagnostic, I've never even given it another thought.

Yea I didn't consider testing either until my blood and biopsy diagnosed DD had hers done and was told her diagnosis was false. Since not all celiacs are automatically tested for genes on diagnosis I think there are a lot more than just the two most common that are associated with celiac. Doctors just don't realize it yet.