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Rachel--24

Who Knows What Their Genes Are?

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I wonder if the Celiacs that have primarily neuro. symptoms are carrying the DQ1 gene along with their Celiac gene....I'm betting they are. I'm thinking DQ2=GI symptoms and DQ1=neuro symptoms. When both genes are present its probably the DQ1 symptoms that are more pronounced. Thats just a guess though.

Hubby is a biopsy proven coeliac but I think he is in this category although he's never actually had his genes tested.

I'd bet he has DQ2 and DQ1.

Looking back in the years before his dx of celiac disease his predominant symptoms were never GI ones.

It started with crippling fatigue - 'flu' like symptoms that didn't go away for years,brain fog, a complete 'slowing down' of mental abilities (he used to be so sharp and quick) weakness in all muscles.

More disturbingly he started to 'stagger' (like he was drunk) loss of co-ordination - pain and tingling in feet and legs ,swelling of feet and lower legs.

Throughout this time he did not suffer with diarrhoea or constipation but he did lose some weight as he just felt so ill he didn't want to eat.

About 2 months before he got dx with celiac disease he had a 2 week spell of diarrhoea which finally made the gastro doc start investigations which resulted in finding villous atrophy.

After starting the gluten-free diet any GI symptoms settled down but the 'staggering' the tingling and swelling still persisted.

At 6 months gluten-free a biopsy revealed no recovery of the villous atrophy and he was put on steroids.

It was only then that neuro symptoms seemed to slowly disappear -however further biopsies have shown that his villi still aren't growing back (?)

Hmmm a mystery indeed :blink:

...and I wonder if a combination of DQ1 and DQ2 predisposes you to 'slow healing' or 'refractory' coeliac???

I would love to know what hubby's genes are...just to satisfy my own curiosity.

There's not many coeliacs (well,not biopsy proven ones anyway) that had the level of neuro problems he had :blink:

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This is very interesting to me as well. I had the gene testing done recently, and it showed both DQ2 and DQ1. I have both neuro and Gi symptoms.

For close to 20 years, I had mostly nausea, and anemia. There was always a sense of a "weak stomach".

This began to change drastically about 3 years ago. I began to have D more, and then I began to have symptoms like tingling in my face, legs and feet. Sometimes my face would feel numb. I had the feeling that my tounge was too large for my mouth--and had trouble getting some words out. I noticed I was clumsier than normal. When I would walk, sometimes I would not know quite where to put my foot--I actually stumbled at times. I developed a slight tremor in my left hand--and my left arm had an altered sensation that is hard to explain.

I began to have days where I didn't want to go anywhere--some days it was all I could do to get out of bed. I realized that I was depressed--and my anxiety, which had always been there--but mild--became a constant, nagging, conflict in my head.

The anemia became severe--I came to a point in 2003 where I couldn't drive--my husband had to take me to the doctor and do the grocery shopping. My doctor did the standard blood and stool tests, and of course, other than the anemia, and a couple of other slightly out of range results--nothing showed up.

After this, the D became chronic--it seemed like everything I ate went right through me. I was exhausted, and for the first time in my life--I lost weight without trying. 15 pounds kind of fell off in just a couple months. My hair began to fall out, and I was scared to death by this time.

I ended up doing my own research after an alternative practioner told me to avoid certain foods--including wheat, oats, barley and rye. First I had ever heard of gluten. But, it led me to a gastroenterologist who took my concerns seriously. It makes me mad that I had to be the one to come up with the idea of Celiac.

So, this is my long-winded way of saying that I have both genes, and both sets of symptoms. An interesting thing, though. I've been gluten-free now for about 18 months. I seem to be bothered less now, when glutened, by the GI issues--and more by the neuro ones. The last time I was CC'd, I had loose stools (not even D) for a couple days, and some nausea, but I was paranoid, edgy, anxoius, and generally not nice to be around--and these lasted much longer, and were much more bothersome.

I wonder if my symptoms are changing because my intestines are healing, but the neuro symptoms will stay as strong as ever? I don't know--I seem to be constanty evolving with this whole thing.

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From what I've been reading this morning (here), it would seem likely that those with neurological manifestations of gluten intolerance have the dq1 gene. It wouldn't surprise me if this became another known celiac gene.

Laura,

To find out your other gene you would need to do the enterolab gene test. As far as I know they are the only ones that test for all the genes.

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I wonder if the Celiacs that have primarily neuro. symptoms are carrying the DQ1 gene along with their Celiac gene....I'm betting they are. I'm thinking DQ2=GI symptoms and DQ1=neuro symptoms. When both genes are present its probably the DQ1 symptoms that are more pronounced. Thats just a guess though.

I'm double DQ1, I get some neuro symptoms, even off gluten :blink: , but when I get gluten, my GI symptoms are VERY bad. Until recently, my GI symptoms were resolved just being gluten-free, but my neuro symptoms and fatigue were not. I'm having GI symptoms again.

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From what I've been reading this morning (here), it would seem likely that those with neurological manifestations of gluten intolerance have the dq1 gene. It wouldn't surprise me if this became another known celiac gene.

I dont think that DQ1 would ever become a "Celiac" gene...not unless they were to change the whoe description of what confirms Celiac Disease. Right now it is destruction of the villi....and DQ1 does not seem to have this affect on the villi. I only know of one person to have a positive biopsy with the DQ1 genes....so it would be very rare.

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I'm double DQ1, I get some neuro symptoms, even off gluten :blink: , but when I get gluten, my GI symptoms are VERY bad. Until recently, my GI symptoms were resolved just being gluten-free, but my neuro symptoms and fatigue were not. I'm having GI symptoms again.

Carla....I think its hard to determine what causes what when there are other conditions involved. I actually did not notice any GI symptoms in myself until after I went off gluten. Then all of a sudden I had GI stuff going on....at that time I only went off gluten for 2 weeks....when my boyfriend at the time first told me about Celiac. I was just trying the diet for a couple weeks. For whatever reason...from that point on the GI symptoms became very apparant and I lost 25 lbs when I went back to eating normal foods. Looking back I did have alot of bloating going on in the very beginning but I didnt pay attention or care because the nerological symptoms were so severe and debilitating...a little bit of bloating meant nothing to me.

I still have both neuro and GI symptoms but to a much lesser degree and definately not caused by gluten. Just being exposed to chemicals can bring on all the neuro symptoms and even some GI stuff like nausea.

Actually is nausea a GI symptom?? :huh:

There was definately a shift for me at some point though....I went from 2 years of primarily having neuro symptoms.....to then having GI stuff become the primary concern. Now it is mainly neurological but the GI problems are still there...I just have to be very careful with what I eat.

So, how does DQ8 fit in...I am a DQ8. I don't have DQ2, but I don't know if I have DQ1.

anyone, anyone? :)

Laura,

I never really read much about the celiac genes since I dont have either of them myself. I dont know anything about DQ8. :(

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Rachel, for me it was the GI symptoms and the weight loss that led me to look for answers. Prior to that, I didn't notice the brain fog because it was so normal for me. I think you're right, when there are other issues, it's hard to determine what comes from what problem ... and right now I have both GI and brain fog issues but am completely gluten-free. I'm certain if I ate gluten, I would be even sicker, as whenever I got glutened in the past, that is what happened. I would bet I probably could cut out more foods, as you have done, and feel better, I just haven't gotten the motivation to do that yet, but I'm getting there. I'm more interested in getting the real answer. It just doesn't seem right that a person would become sensitive to so much for no reason.

Odors can make me very nauseous. We've had to move to a different seat in the movie theater, for example ... but it's not bad enough to keep me at home. I can hardly stand some smells in the grocery store in certain aisles ... it would be hard to work there! ;)

All that being said, when I went gluten-free, for several months, I had no GI issues, it's only recently that they've come back.

I just hope there are some docs out there doing research as interested in having answers as we are.

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This began to change drastically about 3 years ago. I began to have D more, and then I began to have symptoms like tingling in my face, legs and feet. Sometimes my face would feel numb. I had the feeling that my tounge was too large for my mouth--and had trouble getting some words out. I noticed I was clumsier than normal. When I would walk, sometimes I would not know quite where to put my foot--I actually stumbled at times. I developed a slight tremor in my left hand--and my left arm had an altered sensation that is hard to explain.

Patti....I had all of these symptoms except the D. All of these symtpoms were really bad but even more disturbing was whatever was happening to my brain. It was brainfog to the max....I couldnt even drive safely. I had what Nikki describes as a complete slowing down of mental abilities....I couldnt even follow a conversation and alot of the times I couldnt get my words out right. It was very scary. Its obviously better now or I wouldnt be participating in this discussion. :)

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ok ladies, help me out : (andrea, i was tested by enterolab, so here are my results)

i have:

HLA-DQB1*0302 (which is commonly referred to as HLA-DQ8, a celiac gene)

and

HLA-DQB1*0501 (which I cant quite figure out)....so which one is this? help a girl out :) is that dq1?

found this-thought it was interesting: (on wikipedia)

Note on DQ Sertoype Names in Relationship with Allele Names

DQ sertoypes are usually a recognition of Beta chain isoform groups For example, DQ2 = alleles that start with DQB1*02 (*0201, *0202, and *0203).

--DQ2 is encoded by alleles that start with DQB1*02

--DQ4 is encoded by alleles that start with DQB1*04

There two exceptions worth noting:

-DQ1 is 'split' into DQ5 and DQ6, in this case the DQB1 alleles start with

--DQ5 encoded by by alleles that start with DQB1*05

--DQ6 encoded by by alleles that start with DQB1*06

DQ3 is split into DQ7, DQ8, and DQ9, but allele retain DQB1*03.

--DQ7 = DQB1*0301 (or very similar alleles)

--DQ8 = DQB1*0302 (or very similar alleles)

--DQ9 = DQB1*0303 (or very similar alleles)

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

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ok ladies, help me out : (andrea, i was tested by enterolab, so here are my results)

i have:

HLA-DQB1*0302 (which is commonly referred to as HLA-DQ8, a celiac gene)

and

HLA-DQB1*0501 (which I cant quite figure out)....so which one is this? help a girl out :) is that dq1?

I have these same genes. I think the second one is DQ1 with a subtype of 5.

So I think I have the DQ1 and DQ8 genes. My symptoms were neurological, mostly depression, anxiety, irritability, brain fog, etc. My leg would also suddenly give out on me. I'm hoping that was a gluten symptom and not something else but I don't know for sure. It hasn't happened in a while, though.

After going gluten-free, I realized I had been constipated and bloated for years. I just thought that was normal for me.

I think I have recovered completely, but I wasn't aware that I was sick before. I only tested myself because of my daughter and was pleasantly surprised to see my neurological symptoms go away. I also did have to give up casein.

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I would bet I probably could cut out more foods, as you have done, and feel better, I just haven't gotten the motivation to do that yet, but I'm getting there. I'm more interested in getting the real answer. It just doesn't seem right that a person would become sensitive to so much for no reason.

Yeah...it didnt make sense to me either...especially since it came on so suddenly. Unfortunately getting a real answer was the hardest part....I didnt realize when all of this started that I wouldnt get help from the Dr.'s...that I would have to figure it out mostly on my own with the help of some great people on the internet. :)

Interestly...about the smells. I was reading on the Lyme board...alot of people have this problem with smells. They were describing "phantom smells"....where they are smelling things very strongly but nothing is there. I have this happen to me ALL the time!! :o

Its the weirdest thing ever....I "hallucinate" smells. :huh:

I was never sensitive to smells before all of this but now its unbelievable how sensitive I am. Some smells are good though. When I'm at work I love it when someone uses the coffee grinder...especially vanilla flavor. :)

HLA-DQB1*0302 (which is commonly referred to as HLA-DQ8, a celiac gene)

and

HLA-DQB1*0501 (which I cant quite figure out)....so which one is this? help a girl out :) is that dq1?

Laura,

My genes are HLA-DQB1*0301, 0501

I was told that this means I have DQ3 and DQ1.....does anyone know if that is correct? :unsure:

I dont know how to read the genes and the sub-types.....its confusing to me so I never tried to learn more about it.

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Ladies, (since we are mostly ladies) I'd like to remind you that the "one gene, one trait" theory has been shown not to be valid. For example, look at the preponderance of women on this forum. Women are more likely to develop autoimmune symptoms to anything.

It's a lot of fun to speculate the contributions of different HLA genes to our different symptoms, but it isn't the whole story.

If any one is really interested I can't start into some examples for you, but the main point is that your immune system is complex, dangerous (it does protect you), and has intertwined regulatory mechanisms. If something gets past one or two of the regulatory mechanisms (like gluten or Lyme disease) it doesn't get past all of them. You may have HLA genes that predispose you to neurologic symptoms when infected with Lyme, but your other systems keep it from harming you.

Rachel, what if your response to gluten is constipation, and your response to Lyme is diarrhea? As long as you were triggering both response you would have no gastro- issues. When you removed one of the triggers you allowed the other one to take over.

Why do so many of us develop other food sensitivities after stopping gluten? What if being turned on immunogenically by the gluten was keeping the reactions to other foods suppressed?

Sorry, I'll climb down off my soapbox now...

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This is copied from Enterolab's email to me--

Gluten Sensitivity Gene Test

HLA-DQB1 Molecular analysis, Allele 1 0201

HLA-DQB1 Molecular analysis, Allele 2 0502

Serologic equivalent: HLA-DQ 2,1 (Subtype 2,5)

It looks like, and they say I have one of each of these. Then they say that because I have "two copies"...I've never really understood that. Maybe there is some clue in the other numbers?

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rachel: I'm working on it, and get back to you asap. i know there are numerous people on here who have misinterpreted their results because of the way they are presented on enterolab's results page....that being said, I'm not saying you have or haven't, haha!

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I also wanted to say that I get the same type of reactions from smells that Carla and Rachel do. The laundry isle is especially difficult. I usually take a deep breath and go down there and get what I need and get out fast. :D

Church is bad (from a smell standpoint), too. So many different perfumes, after shave lotions, etc. all mingling in the same room. It makes me nauseous. Also makes me cough :angry:

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I'm going to be very blunt and offer up that I don't fully understand. I think I'm going to be calling enterolab again.

my full one:

HLA-DQB1 Molecular analysis, Allele 1 0302

HLA-DQB1 Molecular analysis, Allele 2 0501

Serologic equivalent: HLA-DQ 3,1 (Subtype 8,5)

HLA gene analysis reveals that you have one of the main genes that predisposes to gluten sensitivity and celiac sprue, HLA-DQ2 or HLA-DQ8. Each of your offspring has a 50% chance of receiving this gene from you, and at least one of your parents passed it to you. You also have a non-celiac gene predisposing to gluten sensitivity (DQ1 or DQ3 not subtype 8). Having one celiac gene and one gluten sensitive gene, means that each of your parents, and all of your children (if you have them) will possess at least one copy of a gluten sensitive gene. Having two copies also means there is an even stronger predisposition to gluten sensitivity than having one gene and the resultant immunologic gluten sensitivity or celiac disease may be more

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Why do so many of us develop other food sensitivities after stopping gluten? What if being turned on immunogenically by the gluten was keeping the reactions to other foods suppressed?

Jestgar,

I seriously would pay good money for an answer to that! :D

Laura,

I got the same paragraph as you did under the results. Word for word.

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ok ladies, help me out : (andrea, i was tested by enterolab, so here are my results)

i have:

HLA-DQB1*0302 (which is commonly referred to as HLA-DQ8, a celiac gene)

and

HLA-DQB1*0501 (which I cant quite figure out)....so which one is this? help a girl out :) is that dq1?

Laura you already posted in a newer post. I was going to say dq 3,1 (subtype 8,5).....you already found that. I don't know about these either.

My genes are HLA-DQB1*0301, 0501

I was told that this means I have DQ3 and DQ1.....does anyone know if that is correct? :unsure:

I dont know how to read the genes and the sub-types.....its confusing to me so I never tried to learn more about it.

Rachel, your first allele is like one of mine so I know that.

DQ 3,1 (subtype 7,5)

Some quotes I have. I think both are from the parent site. I know the second one is.

"Hadjivassiliou says, in "Gluten sensitivity as a neurological illness"

"IgG anti-gliadin antibodies have been the best diagnostic marker in the neurological population we have studied. IgG anti-gliadin antibodies have a very high sensitivity for celiac disease but they are said to lack specificity. In the context of a range of mucosal abnormalities and the concept of potential celiac disease, they may be the only available immunological marker for the whole range of gluten sensitivity of which celiac disease is only a part. Further support for our contention comes from our HLA studies. 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.

Both Dr. Fine, a leading celiac disease researcher, and Dr. Hadjivassiliou have identified the DQ1 marker as predisposing one to a non-celiac gluten sensitivity...which can include all the same symptoms and risks as celiac disease, except there will usually not be villous atrophy on biopsy which is required for a celiac diagnosis. (Dr. Fine suggests DQ1 may be seen in 1-2% of biopsy proven celiac disease.)"

It is becoming obvious to many of us who have personal and professional medical experience with gluten intolerance and celiac disease that the problem of gluten sensitivity is much greater and extends beyond the high risk celiac genes DQ2 and DQ8. Traditionally it is reported and believed by many that if you are DQ2 and DQ8 negative you are unlikely to have celiac disease or ever develop it, though this cannot be said with 100% certainty especially since there are documented cases of celiac disease and the skin equivalent of celiac disease, known as dermatitis herpetiformis (DH) in individuals who are DQ2 and DQ8 negative.

Therefore, knowing your DQ specific serotype pattern may be helpful for several reasons. For example, if you have more than one copy of DQ2 or DQ8, you carry two of the major genes. For example, if you are DQ2/DQ2, DQ2/DQ8, or DQ8/DQ8, a term Scott Adams of www.celiac.com has dubbed a “super celiac” you may be at much higher risk for celiac disease and have more severe gluten sensitivity. Certainly if you are DQ2 and/or DQ8 positive you are at increased risk for celiac disease. After a single copy of DQ2 or DQ8, it appears that DQ7/DQ7 might be next highest risk. Dr. Fine has also noted some other associations of the DQ patterns with microscopic or collagenous colitis, neurologic manifestations of gluten sensitivity and dermatitis herpetiformis, which has been one of the gluten sensitive conditions noted to be, at times, occurring in DQ2, DQ8 negative individuals.

Why some people get celiac Disease or become gluten sensitive is not well understood but certain factors are believed to include onset of puberty, pregnancy, stress, trauma or injury, surgery, viral or bacterial infections including those of the gut, medication induced gut injury or toxicity e.g. non-steroidal anti-inflammatory medications such as aspirin, ibuprofen, etc., immune suppression or autoimmune diseases especially since several of those factors are associated with onset or unmasking of gluten sensitivity in someone who is at risk or not manifesting any recognizable symptoms. There is also well known group of individuals who are termed “latent” celiacs.

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Ladies, (since we are mostly ladies) I'd like to remind you that the "one gene, one trait" theory has been shown not to be valid. For example, look at the preponderance of women on this forum. Women are more likely to develop autoimmune symptoms to anything.

It's a lot of fun to speculate the contributions of different HLA genes to our different symptoms, but it isn't the whole story.

If any one is really interested I can't start into some examples for you, but the main point is that your immune system is complex, dangerous (it does protect you), and has intertwined regulatory mechanisms. If something gets past one or two of the regulatory mechanisms (like gluten or Lyme disease) it doesn't get past all of them. You may have HLA genes that predispose you to neurologic symptoms when infected with Lyme, but your other systems keep it from harming you.

Rachel, what if your response to gluten is constipation, and your response to Lyme is diarrhea? As long as you were triggering both response you would have no gastro- issues. When you removed one of the triggers you allowed the other one to take over.

Why do so many of us develop other food sensitivities after stopping gluten? What if being turned on immunogenically by the gluten was keeping the reactions to other foods suppressed?

Sorry, I'll climb down off my soapbox now...

Jestgar,

Your entire post makes alot of sense to me. If there is one thing I'm learning through my whole experience....its that the immune system is very very complex. One thing gone wrong can lead to a multitude of problems...a snowball effect. The symptoms that develop are likely based on our genetic make-up....there are soooo many genes...not just the ones that we are discussing here that are linked to gluten. Its all very complicated and even moreso when there are several body systems involved.

It makes perfect sense that when eliminating one trigger if there are still other things triggering the immune system...those symptoms would then become more apparrant. I've noticed this myself. I've removed all known triggers from my diet and now my sensitivity to chemicals and the symptoms stemming from that...are much more pronounced. I would say that my reation to gluten would be consitpation rather than diarreah...based on the fact that my whole life I've had constipation...I just thought of it as normal though...I didnt know any different and in every other way I seemed to be in perfect health. I rarely get any D but after going gluten-free I started having more GI symptoms, loose stools and weight loss. This could be due to the symptoms of the Lyme infection....being able to take over with the removal of gluten. Its very likely that the gluten was "balancing" me out so that for a period of time I was not noticing any severe GI problems.

You're right in that each of us are very unique and it wouldnt be reasonable to say that one gene is responsible for a certain manifestation of symptoms in all of us.

Thanks to all of the posts on this thread I'm re-thinking how serious my gluten intolerance may actually be. Even though I believe that without the Lyme I would have remained healthy with no noticeable symptoms from consuming gluten....the fact is that it may very well be *real* now. I intend to remain gluten-free and just concentrate on the Lyme and getting my over-active immune system under control. I know that my mind wont completely rest until I can actually identify gluten as causing some sort of identifiable reaction... thats a test for later on down the road though. ;)

I still would like to repeat the Enterolab results in the future......I think the results would still be interesting for all of the reasons previously discussed. :)

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Ok, I finally think I had a lightbulb :)

I owe this to Andrea's PM, so a HUGE thank you. Something you wrote just shifted my thought process and I get it....I had the answer posted in front of me (from the wikipedia link, go figure, that I posted).

HLA-DQB1 Molecular analysis, Allele 1 0302 which is HLA-DQ3, which split into other alleles, and mine is DQ8.

HLA-DQB1 Molecular analysis, Allele 2 0501 which is HLA-DQ1, which splits into other alleles, and mine is DQ5.

Serologic equivalent: HLA-DQ 3,1 (Subtype 8,5)

found this-thought it was interesting: (on wikipedia)

Note on DQ Sertoype Names in Relationship with Allele Names

DQ sertoypes are usually a recognition of Beta chain isoform groups For example, DQ2 = alleles that start with DQB1*02 (*0201, *0202, and *0203).

--DQ2 is encoded by alleles that start with DQB1*02

--DQ4 is encoded by alleles that start with DQB1*04

There two exceptions worth noting:

-DQ1 is 'split' into DQ5 and DQ6, in this case the DQB1 alleles start with

--DQ5 encoded by by alleles that start with DQB1*05 --DQ6 encoded by by alleles that start with DQB1*06

DQ3 is split into DQ7, DQ8, and DQ9, but allele retain DQB1*03.

--DQ7 = DQB1*0301 (or very similar alleles)

--DQ8 = DQB1*0302 (or very similar alleles)

--DQ9 = DQB1*0303 (or very similar alleles)

Yay. It finally clicked! I actually understand it now. You all probably think I'm slow now, don't you :)

Rachel, based on what you wrote: My genes are HLA-DQB1*0301, 0501

301: You are DQ3, which splits into DQ7.

501: You are DQ1, which splits into DQ5.

Patti, based on what you wrote: 0201, 0502;

0201: DQ2

0502: DQ1, which splits into DQ5

Does this make sense? Please tell me I have not lost my mind.

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You have not lost your mind. :)

That makes sense. That description you found is pretty interesting and understandable.

Glad I could be of assistance even though I didn't really understand it myself. :)

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Does this make sense? Please tell me I have not lost my mind.

:lol:

Laura,

It doesnt make sense to me....only because ever since I have this "Lyme-fog" I dont do well with numbers. :huh: I just stare at them until I get a headache and thats about it. Nothing is registering.:unsure:

This is why I've never even bothered to try to "get" the genes and how they are translated.

When I first got tested and posted my results last year....this is what I was told my another poster.

You have HLA-DQB1*0301, 0501. Yours would be translated as DQ3 (subtype 7) and DQ1 (subtype 5) also.

The gluten intolerance genes are:

any HLA-DQB1*03xx [known as HLA-DQ3 (except 0302 ~this is the celiac gene known as DQ8, and is also known as DQ3, subtype 8)]

any HLA-DQB1*05xx [known as HLA-DQ1]

It seems like you are understanding how to read the genes because you are translating them just as she did.

I have DQ3 (subtype 7) and DQ1 (subtype 5)

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