Gene Information Wanted! Please!

[Peta]

To all you KNOWLEDGEABLE people!!!

Firstly, forgive me if I don't make sense? This question comes from someone who is trying hard to learn!

I have just spent 3 hours searching the net for information on what it means to have BOTH HLA DQ2 Alleles (DQA1*05 and DQB1*02) AND HLA DQ8 Alleles (DQA1*0301 and DQB1*0302)

I can find lots of information on celiac disease the genes but they only speak of having one or the other, or with double of one, or a combination of 1 of each, but what nothing about a person having both DQ2 AND DQ8 and having two Alleles of each?

Just wondering if this is unusual? or common? or of no significance?

Thankyou for your patience...and any information.

Peta

[Ursa Major]

Well, this gene stuff is not one of my specialties. Just looks to me like you come by celiac disease honestly!

[Nancym]

I've got DQ8 (celiac) and DQ1 (gluten sensitivity) and I had symptoms of both, I think. The DQ1 seems to be brain related, I'm not sure if intestinal related. I didn't have a biopsy so don't know how bad things were, I suspect they were a little bad.

Was the A1 a typo? I thought they only looked at the HLA B genes.

[chrissy]

i think that all DQ genes are comprised of two alleles. a double copy of B1*0201 is associated with an incresed risk of celiac. 0505 and 0202 are also markers for celiac. in the DQ8 gene it appears that only the 0302 marker is significant. not positive about this info, but this is what it looked like in the research i did. this genetic stuff can be mind boggling.

[GlutenWrangler]

Do you mean having 4 alleles total? Like 2 alleles of DQ2 and 2 alleles of DQ8?

We only get 2 alleles total, encoded each gene. You could have 2 copies of the DQ2 allele, which is homozygous for that gene. The same goes for DQ8. OR you can have one allele that is DQ2 and the other allele that is DQ8, which is heterozygous for that gene. But total, you get one allele from each parent, so you could never have 2 DQ2's AND 2 DQ8's.

Those patients who have any of the previously mentioned combinations are prone to more severe reactions associated with celiac disease. This is compared with patients who only have one copy of the celiac genes. I hope this helps.

-Brian

[chrissy]

i was wrong when i said that DQ genes have 2 alleles. DQ2 and DQ8 ARE the alleles. the other numbers you are referring to are the haplotypes.

25 (of 75) Most common DR-DQ haplotypes in Caucasian Americans DQ DR-DQ DR DQ Freq

Serotype haplotype B1 A1 B1 %[5] rank

DQ2 DR17-DQ2 0301 0501 0201 13. 1 2

DR7-DQ2 0701 0201 0202 11. 1 3

DQ4 DR8-DQ4 0801 0401 0402 2. 2 12

DQ5 DR1-DQ5 0101 0101 0501 9. 1 4

0102 0101 0501 1. 4 14

0103 0101 0501 0. 5 25

DR10-DQ5 1001 0104 0501 0. 7 21

DR16-DQ5 1601 0102 0502 1. 0 17

DR14-DQ5 1401 0104 0503 2. 0 13

DQ6 DR15-DQ6 1502 0103 0601 0. 7 23

1501 0102 0602 14. 2 1

DR13-DQ6 1301 0103 0603 5. 6 6

1302 0102 0604 0. 7 10

1302 0102 0609 3. 4 22

DQ7 DR11-DQ7 1101 0505 0301 5. 6 5

1104 0505 0301 2. 7 11

DR12-DQ7 1201 0505 0301 1. 1 15

DR13-DQ7 1303 0505 0301 0. 7 20

DR4-DQ7 0401 0303 0301 5. 3 7

0407 0303 0301 0. 9 18

DQ8 DR4-DQ8 0402 0301 0302 1. 0 16

0404 0301 0302 4. 2 8

0401 0302 0302 0. 7 24

DQ9 DR7-DQ9 0701 0201 0303 3. 7 9

DR9-DQ9 0901 0302 0303 0. 8 19

[rez]

Where is the info that states that you are more at risk for Celiac if you carry two of the genes. My son is a double DQ2, but our doctor said that having 2 copies doesn't necessarily mean you have a higher chance of getting Celiac or that it's worse. THanks.

[GlutenWrangler]

Rez,

From the Enterolab website:

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).

-Brian

[chrissy]

that sounds like celiac can be more or less severe (according to enterolab). i thought that you either had celiac or you don't-----you don't have a mild or a severe case of it.

[happygirl]

Was the A1 a typo? I thought they only looked at the HLA B genes.

No, its not a typo. Hopefully this will help explain a little bit---from Dr. Green's book:

"HLA DQ2 and DQ8 are nicknames for genes. They are actually molecules on cells that are encoded by specific alleles of genes. HLA DQ2 (encoded by alleles DQA1*05 and DQB1*02) and DQ8 (encoded by DQB1*0302 and DQA1*03)."

Those patients who have any of the previously mentioned combinations are prone to more severe reactions associated with celiac disease. This is compared with patients who only have one copy of the celiac genes. I hope this helps.

Just a note----this research that you mentioned above has not been published *yet* in a peer-reviewed journal. Also, to my knowledge, he has not done a well-controlled study actually determining this. Not to say this isn't true, per se, but the published researchers, like Dr. Fasano and Dr. Green, have not made these statements.

[GlutenWrangler]

While celiac disease is celiac disease, some people are more sensitive than others to gluten; thus a more severe immunological response to gluten.

Also, it is true that Dr. Fine's research hasn't been peer reviewed. But those of us diagnosed through Enterolab can attest to the fact that Dr. Fine's methods are sound. Dr. Green may be a celiac expert, but he should by no means considered the Doctor with all the answers. I read his book. He goes so far as to say that it is no big deal for a celiac to wear lipstick with gluten in it. That's a complete load of crap. He may be an expert, but he definitely cannot empathize with those of us who are very sensitive to gluten.

-Brian

[Peta]

Thankyou all so much for your valuable information.

I am surprised that if gene testing can, in most cases, rule out the need for regular testing (provided it is negative) then why isn't it used more commonly?

When my nephew and sister were diagnosed with celiac their families were also blood tested but were told they may have to be re-tested at other points in their lives....why not just gene test them so they know who can be ruled out?

Is it a cost thing?

Peta

[chrissy]

gene testing is pretty expensive and insurance may balk at paying for it. it took awhile before our insurance agreed to pay for gene testing on my son who is IgA deficient. we are involved in a celiac study, so our whole family is getting the gene testing done with out cost to us------but i still don't know the results yet.

[Nancym]

Just an interesting side note, I think the reason two genes (some have more than two genes BTW and some only have 1 as was recently discovered) the same can be worse is those genes actually produce enzymes or proteins that the body reacts to. So if you could have double the protein production that your body is reacting to. At least, that was how it was explained in terms of autoimmune diseases.

Open Original Shared Link

But it is also becoming apparent that many diseases appear to be influenced by the number of copies of certain key genes, said Charles Lee, another of the project's leaders at the Brigham and Women's Hospital and Harvard Medical School in Boston, Massachusetts.

"Many examples of diseases resulting from changes in copy number are emerging. A recent review lists 17 conditions of the nervous system alone, including Parkinson's disease and Alzheimer's, that can result from such copy number changes," Professor Lee said.

[GlutenWrangler]

This doesn't say that people have more than 2 genes. How would that be possibe? We only have 2 parents.

[Yenni]

I have one celiac gene and one Gluten sensitive one and EnteroLab said my symptoms can be more severe because of this. I am thinking I had symptoms from both these genes too.

[Yenni]

I am just looking at Dr Fine's DVD "Intestinal Health..And beyond!" and one of the doctors speaking on it said that if you have one gene there is 1x the risk to get the disease but if you have 2 genes it is 4x the risk to get it.

[GlutenWrangler]

That definitely makes sense. I have 2, and my symptoms came on very fast and very severe.

[nora-n]

About more copies than 2:

The genes can also be in trans and cis position. Maybe then there can be two there alone, I do not know.

Open Original Shared Link has something about the genes,

"DQ2 and DQ8 are serotypes defined by immunological reactivity where as DQA1:DQB1 are two-locus haplotypes that are commonly found that result in the serotypes, and any given person can produce 4 DQ molecules, 2 in the cis-haplotype dimer pairing and 2 in the transhaplotype dimer pairing. DQ2.5 and DQ8 produce susceptibility in the cis-haplotype pairing configuration. There is a third pairing of haplotypes, DQA1*0201:DQB1*0202(DQ2.2) / DQA1*0505:DQB1*0301 (DQ7.55) that, when both are found in a single patient, can produce susceptibility to coeliac disease via a trans-pairing of the DQA1*0505-DQB1*0202 gene products (DQ α5-β2 heterodimer) [26]. While DQ2.2/DQ2.5 may have increased susceptibility (capable of producing twice the number of DQ α5-β2)[27], without DQ7.55 and DQ2.5, DQ2.2 is atypically associated with coeliac disease[28].

"

nora

[Lollie]

Hi I have a question.... I am thinking of getting the gene's tests done since I have two little girls. From what I read on the site, Entrolab, if I have 2 genes then I definantly have passed one on to the girls..... Is that correct? I am only considering getting the test so that I know if i should or not get my daughters tested.... I don't want them to go through the pain I have....

Thanks

Lollie

[GlutenWrangler]

Nora,

Cis and Trans molecules have the same chemical formula, but cannot be superimposed upon each other. Hence, each can bond in only certain ways. When we have celiac genes, like DQ2 and DQ8, what we essestially have is the abilitly to make DQ that start a process that harms our bodies. Since the genes can be in the Cis or Trans position, we can produce 4 DQ molecules. Two are in the Cis position, and two and in the Trans position. But we still have only 2 genes. It is only saying that we could make 4 DQ molecules.

Lollie,

Yes, if you have 2 celiac or gluten-sensitive genes, you will definitely pass one on to each of your children. I think what you're planning on doing is a good idea. Good luck.

-Brian

[lonewolf]

Thankyou all so much for your valuable information.

I am surprised that if gene testing can, in most cases, rule out the need for regular testing (provided it is negative) then why isn't it used more commonly?

When my nephew and sister were diagnosed with celiac their families were also blood tested but were told they may have to be re-tested at other points in their lives....why not just gene test them so they know who can be ruled out?

Is it a cost thing?

Peta

Gene testing would rule out Celiac, but wouldn't rule out non-Celiac gluten sensitivity. I had many Celiac symptoms and have improved greatly on a gluten-free diet, but my gene test was negative. To tell someone that they don't need to worry about gluten, because they don't have the Celiac genes isn't necessarily a good thing.

[happygirl]

Brian,

Just a note (and I have been tested through the full panel by enterolab):

your signature says enterolab for Celiac. Dr. Fine specifically notes that his tests measure gluten senstivity, and not Celiac per se.

did you have differet testing done by him, or are you inferring his results relate to Celiac?

[GlutenWrangler]

Yes you're absolutely right that Dr. Fine does not diagnose celiac disease. I was worried that people would think that's what I was saying. But on a side note, the malabsorption test, if positive, indicates intestinal damage and therefore celiac disease. But anyway, the diagnosis for celiac disease was based on a number of cumulative factors, including blood tests, endoscopy results, and Enterolab results. Sorry for the misunderstanding, but no, I didn't mean that Enterolab diagnosed me with celiac disease.

-Brian

[rez]

Remember, Dr. Fine diagnoses EVERYONE with a Celiac or gluten sensitivity gene. There is no scientific, medial reviewed research that states that people with a double copy of DQ2 or DQ8 have a higher chance of Celiac.