Celiac gene....

[Caryn]

Hi all,

I just wanted to share. We recently did genetic testing for celiac through enterolabs and received our results back. Our son has one gene directly associated with celiac sprue and another gene associated with gluten intolerance. The kicker is that he received one from myself and one from my husband and so one of us has the celiac gene (probably me-- I will soon get myself tested).

I wanted to share this because someone out there in cyberspace (maybe just a lurker) will have a child present with tics much like mine did, out of the blue, and if they also have digestive issues themselves, or have a history of it in the family, or ADHD, depression, whatever, this is really a good, viable, first stop option to consider. The test we took cost $149. But there are simple at home tests that you could do by making a skin prick and dropping a few drops of blood onto a strip (much like at home pregnancy tests) for $50. I think they are called biocard.

Someone asked me a while back if I would ever go off the gluten and corn free diet or do it indefinitely. After this test I think we are in it for good.

Cheers.

Caryn

[kim]

Caryn,

 

I bet with all of your knowledge regarding Celiac, that you weren't even surprised.

 

Caryn, can you share which genes those are? You know how I'm looking for genes or mostly areas of different chromosomes, that might be part of this complex. I'm also curious as heck to see if either of these genes are located near any of the EXT genes.

 

Thanks tons for all of your very valuable posts/info.

[Caryn]

Sure, Kim--

Anything for science LOL

 

Tigger has the HLA-DQB gene.

He is subtype 2,2

 

From Enterolabs:

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).

 

Is it possible to tell which parent gave me the celiac or gluten sensitivity gene?

Everyone has two copies (or alleles as they are called scientifically) of every gene in the body; one from mother and one from father. The only way to know if a parent definitely has a gluten sensitive or celiac gene without testing them directly, is if a child has two such genes (having received one from mother and one from father). If only one gluten sensitive or celiac allele is present in a child, there is no way to know if it came from mom or dad. One gene is enough, however, to get clinically significant gluten sensitivity or celiac disease, and from published research, two copies yields an even stronger reaction and hence, potentially more severe gluten-related complications.

[kim]

Caryn,

 

I found this back when you posted your response but didn't know if there was any significance, still don't but it is kind of interesting.

 

These are the genes that suspected to be involved in my son's osterochondroma

 

 

http://www.ncbi.nlm.nih.gov/pubmed/9037597

 

8q24.1 (EXT1),11p11-13 (EXT2), and 19p (EXT-3). The EXT1 and EXT2 genes were isolated recently and show extensive sequence homology to each other.

 

This is an abstract on celiac's

 

http://www.biomedcentral.com/1471-2350/2/12

 

Linkage analysis of HLA and candidate genes for celiac disease in a North American family-based study

 

Genomic searches for CD have been conducted in several European populations. In 1996, Zhong et al. [29] studied 40 affected sib pairs from 11 families, and reported significant linkage at 6p23 and weak evidence at 11p11, 7q31.3, 22cen, 15q26, 5q33.3, 19p13.1 and 19q13.2. Houlston et al

 

I have never been able to find anything more specific on the location of the 19p gene, so I did a search for " EXT gene at 19p" and this popped up. Do you think there is anything to this? Since 8q24 is in the area of one of the EXT genes and 19p13 is metioned in the celiac abstract , I'm wondering if the position of the EXT 19 is going to be found to be in the p13 area?

 

Results: Several potentially important genomic regions were identified, such as 8q24 for hip bone size (logarithm of the ratio of the odds that two loci are linked (LOD) 3.27) and 2p24 (LOD 2.04) for spine bone size. 8q24 may also interact with 19p13 to affect hip bone size. Several sex-specific QTL were also detected, such as 14q21 (LOD 2.94) for wrist bone size in women and 16q12 (LOD 2.19) for hip bone size in men.

 

 

EXT 2) to the short arm of chromosome 19 by linkage to a microsatellite DNA marker at the D19S221 locus,

[kim]

edit double post

 

 

,

[Caryn]

Kim,

I wouldn't have a clue how to interpret genetic markers LOL,

But after having three of the guys genetically screened I will say that scientists have identified a lot of gluten intolerant genes (9) and only 2 are associated with celiac disease. This must mean than the other 9 can be implicated in a whole host of other autoimmune disorders. And you, I think, are thinking along the same lines as myself. For those that are blessed with two gluten intolerant genes that differ, does this make them perfect candidates for particular conditions? You know, like creating "the perfect storm?"

And when you take into consideration mutations, etc....

As far as my guys go, no bony growths have been noted so far, so I'm pretty sure we don't fit into that same category.

Caryn

[kim]

Caryn,

 

Yes, I do think we are thinking along the same lines. From what I understand of the celiac genes, you can have gluten sensitivity without full blown celiac depending on which gene is involved?

 

I think I need to explain something about the bony tumor (I should be saying "overgrowth of cartiledge" tumor). From reading everything that I can get my hands on it appears that these tumors are rare and the theories that I am aware of, in regards to their development are something called LOH or loss of heterozygocity which basically means that you had one bum copy of a gene or allele and something happens to knock out the other working gene or allele and #2. something referred to as "gene dose. "

My point, it sure seems like you could have a mutation in one of these genes, and express NO tumor. As I have said before, my youngest son does not have any tumor either, yet I would think it unlikely that these same genes are not involved.

 

The other thing that may be important to others is the fact that a mutation in these genes results in a lack of N acetylglucosamine. This substance has recently been reported to have astounding (I think that was the word that they used) results in protecting cells from autoimmune reactions.

 

Look at this study

 

http://www.ncbi.nlm.nih.gov/pubmed/2394351

 

Mannan and oligomers of N-acetylglucosamine protect intestinal mucosa of celiac patients with active disease from in vitro toxicity of gliadin peptides.Auricchio S, De Ritis G, De Vincenzi M, Magazzù G, Maiuri L, Mancini E, Minetti M, Sapora O, Silano V.

Department of Pediatrics, II Faculty of Medicine, University of Naples, Italy.

 

Wheat flour and other cereals toxic for celiac patients contain an alcohol-soluble protein fraction that, under experimental conditions simulating in vivo protein digestion, yields peptides that agglutinate undifferentiated K 562(S) cells. In contrast, cereals well tolerated in celiac disease (i.e., rice and maize) do not. Furthermore, purified A-gliadin peptides that damage in vitro-cultured flat celiac mucosa are powerful agglutinins for K 562(S) cells, whereas A-gliadin peptides that do not show any adverse in vitro effect on celiac intestine lack agglutinating activity. Mannan, acetylglucosamine, and its oligomers (N,N'-diacetylchitobiose and N,N',N"-triacetylchitotriose) were able to prevent and reverse cell agglutination induced by peptides from all the toxic cereals. Moreover, mannan and N,N',N"-triacetylchitotriose exhibited a protective effect on intestinal mucosa specimens of patients with active celiac disease cultured with wheat protein-derived peptides. These data are consistent with the hypothesis that the agglutinating and toxic peptides are bound by carbohydrates.

 

http://today.uci.edu/news/release_detail.asp?key=1612

 

This finding shows the potential of using a dietary supplement to help treat autoimmune diseases,” said Demetriou, an assistant professor of neurology, and microbiology and molecular genetics. “Most importantly, we understand how this sugar-based supplement inhibits the cells that attack the body, making metabolic therapy a rational approach to prevent or treat these debilitating diseases.”

 

The UC Irvine study defines how metabolic therapy with the sugar GlcNAc and other related nutrients modifies the growth and autoimmune activitiy of T-cells. Virtually all proteins on the surface of cells, including T-cells, are modified with complex sugars of variable lengths and composition. Recent studies have shown that changes in these sugars are often associated with T-cell hyperactivity and autoimmune disease

http://www.newscientist.com/article.ns?id=mg19426074.500

 

I'm astounded by their outcomes," says Nick Giannoukakis, a pathologist at the University of Pittsburgh School of Medicine in Pennsylvania. In 2002, he showed that glucosamine worked as well as standard immunosuppressants in increasing the amount of time transplanted hearts lasted in mice.

 

and

 

Meanwhile, a small study of 12 children with autoimmune inflammatory bowel disease, suggested that GlcNAc lessened symptoms in eight of them

.

 

 

I hope when you get done with your study on HCl, you will take a look at NAG! Would like your take on it.

[sarahp]

Caryn - has the gluten free diet stopped the tics occurring (is corn related to??). Our son also has the celiac gene.

thanks

Sarah

[Caryn]

Caryn - has the gluten free diet stopped the tics occurring (is corn related to??). Our son also has the celiac gene.

thanks

Sarah

Sarah,

Gluten is a major factor for folks with genetic susceptibility like your son and mine. But I think it is only one part of it. Do you know if your son has the autoimmune disorder or just the genetic predisposition? Our G.P. guessed that our son must have full blown celiac because of his genetic testing and his recovery on the diet both digestive and neurological. In the last year he's had so few exposures that I can count them on one hand. I have a gluten and corn free house and I pack food for him EVERYWHERE we go now. It really is no big deal anymore. If he has a class pizza party (like he did last month) I just pack one of Amy's GF frozen pizzas. The party mom just popped it in her oven, problem solved! He has recovered beautifully but it took nearly a year. I myself think he really does have Celiac, but there is no way to know without a biopsy or a blood test after a 30 day trial. We are just not willing to feed him wheat every day for 30 days. I read cases of families with kids on a GFCF diet for Autism who resumed the average diet after recovery only to see regression again. We are not dealing with autism, but I fear the same would happen as far as the tics go. Just my opinion. Each time our son got exposed he got either explosive diarrhea or he vomited after eating. Those exposures were part of my learning curve months. For example, I fed him ham from a deli and he got cross-contamination because the equipment wasn't clean, and also had a ticcing outburst because, probably, the meat was loaded with preservatives and dextrose (corn derived). He also tested positive to a wheat allergy which is another fish altogether. Some Celiac's can eat wheat starch and can touch things made out of wheat no problem. A wheat allergy just makes it harder for sinus issues, etc... His very first tic was a sniffing tic and we never noticed it because before the diet he had chronic sinus issues-- he was a pretty snotty little guy LOL!

 

For us corn is a MAJOR tic trigger. Over time I have come to believe that the heavy wheat, corn, and dairy diet of his toddler years kicked up the Celiac issues and set the stage for turning on the T.S. gene. He may have been Celiac from birth. He was very colicky and I was told to give up dairy myself (I was nursing) due to his digestive issues (gluten, I believe can go through the milk, but double check that!) Anyway, he was always getting infections-- croup was two, three times a year, ear infections, flu's.... During these years I think his gut was being slowly destroyed by the gluten which couldn't be digested because he genetically wasn't producing an enzyme to break it down. Every snack I gave him had gluten in it and many baby jars do too! Eventually his gut was permeated and the proteins got into his blood. A series of vaxs became the catalyst and the neuro effects began when he was 3 1/2.

 

Gut healing takes time and in our experience and from what we've learned from other Celiac folks, the first few months prior to healing of the gut are pretty sickly and reactive. You have to be patient and commit to at least 6 months of strict compliance. This is my strong opinion on it. No cheating, it only compromises the healing and causes regression. It also makes it hard to pinpoint what is causing the tics (as other things can contribute too, as we all know). Once his body healed things were great. Kim and I have talked a lot about liver and pancreatic function and I really believe that these kids have sluggish livers that have a hard time detoxing. This is why they need to be on a junk free diet for success. Gluten free is only part of it. There are a lot of gluten free junk foods that we just don't buy because they have preservatives in them that are not appropriate. We also NEVER use refined sugar. If I have to bake with sugar (which is rare) I use organic evaporated cane juice. My sweeteners of choice are honey and maple syrup.

 

There are a sizeable number of folks who are Celiac and can't handle corn either. It's possible that corn is a major trigger for your son too, but that may not be the case either. I will say that in my opinion that corn is too prevalent in this country and is a known inflammatory food. It would be best to cut back on it for everyone, but unless you know whether or not there is an allergy, it may or may not make a difference in the ticcing (but DO try to STAY AWAY from High fructose corn syrup, dextrose, citric acid if you can, and other highly processed corn sweeteners-- many folks on this list in the past have said that HFCS is a major trigger). The more corn is processed the more sulfur it contains, plus the stuff they add to it to process it is pretty toxic to the system. Some folks believe that proteins in general are tough for some Celiacs, that is a whole different can of worms (so they avoid casein (milk protein), soy, corn, and wheat). Sounds pretty crazy and impossible, I know, but we do it and I have tons of recipes and a list of products that we use. We are not deprived and are not starving. I still make Christmas cookies, cake, and many dinner recipes that are common in most homes. Now if there is an exposure (like last month when the teacher accidentally gave my son 3 freeze pops in two days loaded with HFCS and food coloring-- I'm guessing about 8 oz worth) he erupted in a chronic rapid (not slow and exaggerated) eye blinking tic that lasted two weeks and was pretty constant during the waking hours. Now prior to diet he had six or seven tics and some that happened simultaneously, sort of like a choir--- they would roll into each other and be very noticeable. Have you ever read Doris Rapp's "Is this Your Child?"

 

Caryn

http://healthy-family.org/quick-links-to-g...rn-free-recipes

[kim]

So 1 1/2 years later, I return to my genetic notions and I bet anyone who suffered through it before will be really happy

 

First off, I continue to be very interested in glucosamine or N acetyl glucosamine to be more exact, in treatment for autoimmune disorders. I think the article that I referenced in this thread talks specifically about it's usefulness for organ transplantation. On another note, I have had mild psoriasis since my late teens, early 20's. Annoying patch on my elbow has always been the worst of it (fairly mild case) with a small spot near hairline at neck. Last Dec. I scratched my elbow, got an infection and broke out in a horrendous full body rash. Dr. in ER, family physician and derm all said that the "rash" was infection triggered, but that's really all they said. Immediately went to a psoriasis web group to start learning all that I could about Psoriasis. I found out that there is a lot of speculation regarding strep, triggering psoriasis (never knew that). Pubmed is loaded with articles. Also, a fairly strong association with celiac. A dermatologist Calif. has an interesting site about the use of curcumin/turmeric for psoriasis. She refers to it as a genetic defect on chromosome 6. 6p21 has been frequently associated with psoriasis.

 

Last night I found this new reseach regarding TS. bolding mine

 

http://archneur.ama-assn.org/cgi/content/s...6/10/1267?rss=1

 

Conclusion Variants in BTBD9 that predispose to restless legs syndrome and periodic limb movements during sleep are also associated with TS, particularly TS without obsessive-compulsive disorder. [cis]

 

So, I looked up the chromosome location

 

http://www.ncbi.nlm.nih.gov/IEB/Research/A...man&l=BTBD9

 

BTBD9 Gene Card

Map: This gene BTBD9 maps on chromosome 6, at 6p21 according to Entrez Gene.

 

Then, I looked at this from wiki

 

http://en.wikipedia.org/wiki/HLA-DQ

 

HLA-DQ (DQ) is a cell surface receptor type protein found on antigen presenting cells. DQ is an αβ heterodimer of the MHC Class II type. The α and β chains are encoded by HLA-DQA1 and HLA-DQB1, respectively. These two loci are adjacent to each other on chromosome 6p21.3. Both the α-chain and β-chain vary greatly. A person often produces two α-chain and two β-chain variants and thus 4 DQ isoforms. The DQ loci are in close genetic linkage to HLA-DR but less closely linked to HLA-DP, HLA-A, HLA-B and HLA-C.

 

DQ functions on antigen presenting cells, and is an antigen presenting molecule. Different DQ isoforms can bind to and present different antigens to T-cells. In this process T-cells are stimulated to grow and can signal B-cells to produce antibodies. DQ functions in recognizing and presenting foreign antigens (proteins derived from potential pathogens). But DQ is also involved in recognizing common self-antigens and presenting those antigens to the immune system in order to develop tolerance from a very young age.

 

When tolerance to self proteins is lost, DQ may become involved in autoimmune disease. Two autoimmune diseases in which HLA-DQ is involved are coeliac disease and diabetes mellitus type 1. DQ is one of several antigens involved in rejection of organ transplants.

 

Pretty interesting hau?

[mylittleangel]

So 1 1/2 years later, I return to my genetic notions and I bet anyone who suffered through it before will be really happy

 

First off, I continue to be very interested in glucosamine or N acetyl glucosamine to be more exact, in treatment for autoimmune disorders. I think the article that I referenced in this thread talks specifically about it's usefulness for organ transplantation. On another note, I have had mild psoriasis since my late teens, early 20's. Annoying patch on my elbow has always been the worst of it (fairly mild case) with a small spot near hairline at neck. Last Dec. I scratched my elbow, got an infection and broke out in a horrendous full body rash. Dr. in ER, family physician and derm all said that the "rash" was infection triggered, but that's really all they said. Immediately went to a psoriasis web group to start learning all that I could about Psoriasis. I found out that there is a lot of speculation regarding strep, triggering psoriasis (never knew that). Pubmed is loaded with articles. Also, a fairly strong association with celiac. A dermatologist Calif. has an interesting site about the use of curcumin/turmeric for psoriasis. She refers to it as a genetic defect on chromosome 6. 6p21 has been frequently associated with psoriasis.

 

Last night I found this new reseach regarding TS. bolding mine

 

http://archneur.ama-assn.org/cgi/content/s...6/10/1267?rss=1

 

Conclusion Variants in BTBD9 that predispose to restless legs syndrome and periodic limb movements during sleep are also associated with TS, particularly TS without obsessive-compulsive disorder. [cis]

 

So, I looked up the chromosome location

 

http://www.ncbi.nlm.nih.gov/IEB/Research/A...man&l=BTBD9

 

BTBD9 Gene Card

Map: This gene BTBD9 maps on chromosome 6, at 6p21 according to Entrez Gene.

 

Then, I looked at this from wiki

 

http://en.wikipedia.org/wiki/HLA-DQ

 

HLA-DQ (DQ) is a cell surface receptor type protein found on antigen presenting cells. DQ is an αβ heterodimer of the MHC Class II type. The α and β chains are encoded by HLA-DQA1 and HLA-DQB1, respectively. These two loci are adjacent to each other on chromosome 6p21.3. Both the α-chain and β-chain vary greatly. A person often produces two α-chain and two β-chain variants and thus 4 DQ isoforms. The DQ loci are in close genetic linkage to HLA-DR but less closely linked to HLA-DP, HLA-A, HLA-B and HLA-C.

 

DQ functions on antigen presenting cells, and is an antigen presenting molecule. Different DQ isoforms can bind to and present different antigens to T-cells. In this process T-cells are stimulated to grow and can signal B-cells to produce antibodies. DQ functions in recognizing and presenting foreign antigens (proteins derived from potential pathogens). But DQ is also involved in recognizing common self-antigens and presenting those antigens to the immune system in order to develop tolerance from a very young age.

 

When tolerance to self proteins is lost, DQ may become involved in autoimmune disease. Two autoimmune diseases in which HLA-DQ is involved are coeliac disease and diabetes mellitus type 1. DQ is one of several antigens involved in rejection of organ transplants.

 

Pretty interesting hau?

 

I am so confused......if my husband has psoriasis, could that mean my son with tics could have PANDAS because they are both autoimmune? I had my son tested for celiac and he was negative.

[kim]

mylittleangle,

 

I don't think one parent having 1 disorder is enough info to go on. I guess I would say to keep looking for a bigger picture. Many parents have psoriasis and their kids don't have tics. You could probably guess though, that I'm thinking psoriasis could be significant in some cases.

 

Have you visited this site yet?

http://www.pandasnetwork.org/

 

There is a table with family history info.

http://www.pandasnetwork.org/fhtable.html

 

Could I ask if your husband has any sign of connective tissue disease associated with the psoriasis (fingernail involvement, psoriasis arthritis, anything?).

[mylittleangel]

mylittleangle,

 

I don't think one parent having 1 disorder is enough info to go on. I guess I would say to keep looking for a bigger picture. Many parents have psoriasis and their kids don't have tics. You could probably guess though, that I'm thinking psoriasis could be significant in some cases.

 

Have you visited this site yet?

http://www.pandasnetwork.org/

 

There is a table with family history info.

http://www.pandasnetwork.org/fhtable.html

 

Could I ask if your husband has any sign of connective tissue disease associated with the psoriasis (fingernail involvement, psoriasis arthritis, anything?).

 

 

No connective tissue disease that I know of. He does clear his throat sometimes but he says it's not a tic. I think it is.

[Caryn]

There is a lot of research on false negative readings on celiac tests in pediatrics. If your child has low IgA then there is a high likelihood that the celiac will be a false negative. Also, celiac gene is associated with MANY autoimmune disorders. Especially DQ2, the more common one.