Genetics Question

[leadmeastray88]

I've been so curious about genetics lately, reading all the gene threads on here, especially since finding out on Kimball's website that DQB1*202 can be associated with Celiac if encoded by alleles DQA1*0501 or DQA1*0505.

I tested with Enterolab and they found DQB1*0202 and call it a "gluten sensitive gene".

I e-mailed Enterolab and asked how they can possibly rule out that DQB1*0202 is not a Celiac gene when they do not test for the alpha part of the gene - Dr. Fine e-mailed me back personally and said "he would need the scientific literature source of this information from Kimball genetics", as he is certain that that gene does not predispose to Celiac.

So my question is this - do any of you genetic buffs out there know of any scientific literature that disproves this? I know it states this directly on the Kimball site but I'd like a piece of medical literature if it is at all possible, or maybe point me in the right direction? I have no clue how to go about researching this.

Thanks in advance!

[ShayFL]

I just started a genetics class with CCNH where I have my Phd. I am excited to learn more. I read today that they have now discovered 26 genes related to the most common form of lung cancer. There is NO WAY that just 2 genes are responsible for ALL Celiac cases. I think if they put some money and resource into it, they will discover MANY other genes for Celiac. In fact, Europe and Asia recognize 7 or 8. We are just lagging behind........

[Jestgar]

Here is what you get when you search pubmed. Some of the articles are free, others you may get access to at a university library.

Open Original Shared Link

[leadmeastray88]

Here is what you get when you search pubmed. Some of the articles are free, others you may get access to at a university library.

Open Original Shared Link

Thank you so much - all of those articles were so helpful.

I forwarded the link to Dr. Fine so it'll be interesting to see what he says

[leadmeastray88]

UPDATE:

Dr. Fine and I have been emailing each other back and forth all day.

He has noted that a couple of months ago they discovered that DQB1*0202 can exacerbate the effect of an associated 0201 gene, and/or is also present in about 1% of Celiacs. He said they will be making the distinction in the coming testing.

Still, the litterature Jestgar provided seems to suggest it is more common than that. I'm thinking I'll get Kimball testing to test for the alpha portion of the gene.

[climbmtwhitney]

Hi.

Curious. I keep hearing that they recognize 7 or 8 Celiac genes in Europe. But, I searched and can't find the info. Does anyone have a link to those 7 or 8 genes (one that the average Joe can understand)? Or, can someone list them?

I'm curious because 2 of my children and my husband are double DQ1 and have been diagnosed gluten intolerant. And, of those 2 children ONE has the anti-tissue transglutaminase antibody that is 96% specific to Celiac. My 3rd child (oldest) and I have been diagnosed Celiac (biopsy on me, genes, symptoms, response, and Enterolab). It seems that my littlest one shouldn't have the anti-tissue transglutaminase antibodies like my oldest and I, if it's not actually Celiac. Then the doctor scared me when she said we need to test for Juvenile Diabetes since that's one of the diseases in which anti-tissue transglutaminase antibodies can show up. So, I'm wondering if he may actually have Celiac too, just different Celiac genes. I WON"T do the biopsy on any of them because it's invasive and not worth putting them back on a gluten diet. Plus my son had difficulty waking from anesthesia after his ear tubes. And, there has been such an improvement after going gluten-free. So.....really curious if DQ 1,1 is considered "Celiac" in Europe.

Thanks! Everyone here is SO helpful!

Sonya

[Rachel--24]

In fact, Europe and Asia recognize 7 or 8. We are just lagging behind........

I have to wonder about this since the majority of people who actually test positive for the disease (i.e. positive bloodwork and/or biopsy) DO have at least one of the main genes (DQ2 or DQ8). The percentage who do not have those genes is very small.

Even if we recognize 100 genes as being involved in Celiac Disease here in the US....is it really going to change anything with regards to who tests positive for Celiac Disease? I think we would still find that somewhere around 98% of those who test positive carry one of the main genes.

[happygirl]

"Within the group of patients with neurological disease and gluten sensitivity (defined by the presence of anti-gliadin antibodies) we have found a similar HLA association to that seen in patients with celiac disease: 70% of patients have the HLA DQ2 (30% in the general population), 9% have the HLA DQ8, and the remainder have HLA DQ1. The finding of an additional HLA marker (DQ1) seen in the remaining 20% of our patients may represent an important difference between the genetic susceptibility of patients with neurological presentation to those with gastrointestinal presentation within the range of gluten sensitivity. "

from: Journal of Neurology Neurosurgery and Psychiatry 2002;72:560-563

Gluten sensitivity

Gluten sensitivity as a neurological illness

M Hadjivassiliou, R A Gr

[leadmeastray88]

"Within the group of patients with neurological disease and gluten sensitivity (defined by the presence of anti-gliadin antibodies) we have found a similar HLA association to that seen in patients with celiac disease: 70% of patients have the HLA DQ2 (30% in the general population), 9% have the HLA DQ8, and the remainder have HLA DQ1.

I'm wondering HLA DQ2 what? DQ2 in general or are there specific DQ2s that associate with the disease?

[nora-n]

Go to wikipedia and HLA DQ2, there are more DQ2 than the most common 2,5 and the less associated 2,2. There are even other DQ2 but I think this is more speculative.

About the question about europe and other genes, I have collected some links to articles and abstracts where they found DQ1 celiacs, DQ7 and DQ9 celiacs. Open Original Shared Link this above one I have not listed yet, but Hadjivassiliou has written in several papers on gluten ataxia that about 20% of his gluten ataxia patients ar DQ1.

Those references on DQ1, DQ7 and DQ9 are not on wikipedia under the specific HLA genes.

That leaves only DQ4 as not connected to celiac.

Nora

[ShayFL]

Apparently saying that Europe recognizes 7 other genes up to 9 is a bit misleading (I made the mistake myself).....they have discovered 7 new genetic regions....but not specific genes. The research is ongoing and will certainly change the way we look at Celiac with regard to genetic testing:

Open Original Shared Link

[veggienft]

Go to wikipedia and HLA DQ2, there are more DQ2 than the most common 2,5 and the less associated 2,2. There are even other DQ2 but I think this is more speculative.

Here's how I understand it.

DQ2 is the most common gene in intestinal celiac disease. I think there are three iterations of it. As I understand it, that simply comes from the way antibodies are spliced and replicated from portions of chromasomes. It's referred to as "gene dose".

For antibodies, there's an alpha side and a beta side. The beta side is longer, and sticks out the end of the antibody. It does most of the work .......different work in different situations. So the beta side is more associated with the effects and side effects.

But an antibody's alpha side still has an effect. It's just less prominent.

* The strongest DQ2 celiac effects are in people with DQ2 genes on both sides, alpha and beta. That's commonly referred to by the nickname DQ2.5.

*The second strongest DQ2 celiac effects are in people with a DQ2 beta gene, and some other DQ alpha gene. That's commonly referred to by the nickname DQ2.2.

*The weakest DQ2 celiac effects are in people with some other DQ beta gene, and a DQ2 alpha gene. Generally, I think doctors and labs don't test for this matchup. They should.

I'm sure somebody will correct me if I'm wrong.

..

[fedora]

well.

It is medically known the DQ2.2 and the correct alpha part from certain DQ7s make the whole celiac gene DQ2.5. I wonder why DR. Fine does not know this or does not care. Either way he does not report it to the people who have both DQ2.2 and DQ7. Of course in those cases, his DNA testing of only the beta parts is not effective enough. Then someone has to go get alpha testing done too.

I have DQ2.2 and DQ5. I am glad I know that I have DQ5. I know it has been linked with neurological issues and gluten intolerance. Since I do not have DQ7, it is not necessary for me to get further testing of the alpha parts of the gene.

I Never had the celiac blood tests or biopsy. When I gave up gluten it was after being on a predominately wheat free diet for years(except I cheated sometimes). Plus I knew nothing about the traditional tests. A few days into it I KNEW it was changing me. I read about the traditional tests and was unwilling to go back on a wheat filled gluten filled diet to try it out. My symptoms were Low blood pressure, dizziness, itching and bumps on buttocks, itching on my sides and in armpits, exczema on both hands, constipation alternating with pooping tons, naseau, brain fog, vision changes, hemeroids, anemia, and nightmares. I have had tremendous or complete improvement in these symptoms. I have also had improvement in my depression and emotional pms. For several months after going gluten free I had no depression or emotional pms and my cycles were perfectly 28 days each. Something messed me up though and I have been having mood issues and messed up cycles again:( Also as a kid I had joint pain, terrible diahrea, vomiting, and a bone scan revealed I never used up my entire growth plates. HMMm

It is hard for me because I got the gene testing to help see if I had celiac or not. I got a Usually not but sometimes gene. hmmmm

take care

[leadmeastray88]

Thanks so much guys for your replies

Quick question:

HLA-DQB1 Molecular Analysis, Allele 1 0202

HLA-DQB1 Molecular Analysis, Allele 2 0301

Serologic equivalent: HLA-DQ 2,3 (Subtype 2,7)

What does the "subtype" mean? 2 and 7, does that mean I am DQ2 and DQ7?

[Jestgar]

Celiac disease and DH are thought to be multifactorial:

Open Original Shared Link

Open Original Shared Link

The MHC molecules function as immunoprotective agents:

Open Original Shared Link

Open Original Shared Link

Open Original Shared Link

HLA genes function as antigen presentors, meaning they hold up a piece of protein for an immunocompetent cell to look at and decide if it's good or bad (see wiki above). The HLA protein itself is made up of two subunits; alpha and beta. These proteins are each encoded by a different Open Original Shared Link, and each can have common mutations (single nucleotide polymorphisms, or SNPs) Open Original Shared Link. The different SNPs have slightly different effects on the structure of the receptor protein, which can affect the type of protein piece it's willing to hold up for inspection.

Most people with Celiac disease have on of 2 HLA types:

Open Original Shared Link

There is no evidence that these HLA types, or any other specific gene cause Celiac disease (see OMIM links), they are only associated.

Open Original Shared Link are produced by a different type of cell. Each antibody recognizes only one type of protein. When you are exposed to a virus (for example) the virus is ingested by one type of cell, chewed up, and little pieces are held out for other cells to look at. If a passing cell has, on it's surface, a receptor that recognizes that piece of protein, it begins replicating, and soluble (not membrane bound) antibodies are made that also recognize the foreign protein.

In autoimmune disease, for reasons unclear, the body stops recognizing some of it's own proteins and begins attacking them.

Bottom line: ASSOCIATED does not equal CAUSES

If you plan to argue this point, please look up 'oversampling in populations' and 'Eigenstrat correction' which I don't believe has been done regarding the HLA DQ question (it just means that if a certain population has an over-representation of a gene when compared to another population, looking at disease states in these populations can correlate gene-to-disease, but without foundation (they have more of the gene in general, has nothing to do with the disease)).

[Jestgar]

Thanks so much guys for your replies

Quick question:

HLA-DQB1 Molecular Analysis, Allele 1 0202

HLA-DQB1 Molecular Analysis, Allele 2 0301

Serologic equivalent: HLA-DQ 2,3 (Subtype 2,7)

What does the "subtype" mean? 2 and 7, does that mean I am DQ2 and DQ7?

Open Original Shared Link

[fedora]

yes.

you are DQ2 subtype 2 and DQ7.

DQ7 is a subtype of DQ3, but is referred to as DQ7.

the DQ types are

DQ1 divided into DQ5 and DQ6

DQ2 divided into DQ2 subtype 1 and DQ2 subtype 2

DQ3 divided into DQ7, DQ8, and DQ9

DQ4

so I am DQ2 subtype 2 and DQ5( which is a DQ1)

My daughter is a double DQ1. She is DQ5(from me) and DQ6(from dad)

[Alizarin]

Thanks so much guys for your replies

Quick question:

HLA-DQB1 Molecular Analysis, Allele 1 0202

HLA-DQB1 Molecular Analysis, Allele 2 0301

Serologic equivalent: HLA-DQ 2,3 (Subtype 2,7)

What does the "subtype" mean? 2 and 7, does that mean I am DQ2 and DQ7?

Hi! I know this is an old thread, but I've just received Enterolab gene test results and I have the exact same one as you. Did you end up finding out more about it? And if so, would you mind sharing? Thanks so much!!!

[mushroom]

I wanted to let you know this is a rather old post