Interpreting raw DNA: HLA-DQ2.2?

[FlyingWotsitThingy]

Hello - apologies if this is against the rules as I’ve only just joined this forum. Just to be clear, I am NOT looking for any kind of absolute diagnosis - merely looking to understand the genetics behind celiac and understand if I can rule it out before embarking on an what might be an unnecessary and difficult gluten challenge.

 

I don't seem to have the variants for HLA-DQ2.5 or HLA-DQ8, however I am unsure how to interpret my results for HLA-DQ2.2 as I'm not smart enough to understand the scientific papers surrounding this and there seems to be conflicting information on the web! I know there are three places to look, but do you need markers for all three to have this, or is one or two enough to cause a problem? My results are rs4713573 AA, rs2395182 TT and rs7775228 TT and I can't figure out what this actually means.

 

I had the DNA test done through 23andMe, and then imported the raw data into Promethease, however I am having trouble understanding that as well. When I type in celiac in the Promethease search bar, I get an awful lot of results, including:

 

SH2B3 rs3184504 CT (increased risk)

REL rs2816316 AC (increased risk)

IL-18 rs917997 and rs6441961 both CT (slightly increased risk)

FUT2 rs601338 AA (increased risk)

 

Are these an indication that I could be at risk of developing celiac, or would these only increase the risk if I also had genes for HLA-DQ2.5, HLA-DQ8 or HLA-DQ2.2? Massive thanks to anyone who can help!

[cristiana]

Hello FlyingWotsitThingy!

Welcome to the forum. 

I cannot pretend to know anything about those DNA results - it looks incredibly complicated, so I can understand why you are struggling.

I am sure someone on this forum will be able to help but out of interest, is it possible to contact the laboratories who conducted the tests for help.

Also, out of interest, what led you down this road?  Do you have family members with celiac disease or are you symptomatic?

Cristiana

Edited August 5, 2021 by cristiana

[FlyingWotsitThingy]

3 minutes ago, cristiana said:

Hello FlyingWotsitThingy!

Welcome to the forum. 

I cannot pretend to know anything about those DNA results - it looks incredibly complicated, so I can understand why you are struggling.

I am sure someone on this forum will be able to help but out of interest, is it possible to contact the laboratories who conducted the tests for help.

Also, out of interest, what led you down this road?  Do you have family members with celiac disease or are you symptomatic?

Cristiana

Hi Cristiana, thanks for your reply. When eating gluten I am very symptomatic, as is my sister. Around ten years ago my sister and I were diagnosed as “gluten intolerant” through applied kinesiology muscle testing, which I’ve never really been sure is a legitimate practise (it seemed a bit suspect to me) however we both improved very quickly after going gluten free. I’ve often wondered if there’s more to it than just intolerance because of the number and severity of symptoms, however have never managed to get properly tested as I can’t stick to a gluten challenge long enough to get an accurate blood test without feeling terrible, so if my genes say it can’t be celiac I don’t think it’s worth suffering through the gluten challenge to get what will inevitably be a negative blood test, so will be happy to live as if it’s NCGS. 
 

We have a couple of other people in the family with autoimmune disorders (Crohns and psoriasis etc), and I have a couple of cousins who I’m not in contact with who are also gluten free, though I’m not sure if they’ve been diagnosed with celiac or not. 
 

23andMe only test for the main two genes, so probably wouldn’t be able to advise me. I’m not sure about Promethease, so I’ll look into whether they could help with interpretation. 

[trents]

41 minutes ago, FlyingWotsitThingy said:

Hello - apologies if this is against the rules as I’ve only just joined this forum. Just to be clear, I am NOT looking for any kind of absolute diagnosis - merely looking to understand the genetics behind celiac and understand if I can rule it out before embarking on an what might be an unnecessary and difficult gluten challenge.

 

 

May we assume you have already been eating gluten free?

As with Cristiana, I am not an expert on genetics, celiac genetics or otherwise. So I won't attempt to analyze your genetic testing results or offer an opinion . . . except to say that my understanding is that not having either the DQ 2.5 or the DQ8 genetic markers does not rule out the possibility of developing celiac disease. I do know that those two gene markers were linked to Celiac disease through studies done with people of caucasian/European decent and since then there is evidence accumulating to the effect that other races may not show that same affiliation. I just think there is a lot we don't know about the genetics of celiac disease and that it may be a more complex and varied genetic phenomenon than originally thought.

The other thing I would offer is that if you have established the fact through experience that you cannot tolerate gluten then you may have NSGS (Non Celiac Gluten Sensitivity) rather than celiac disease. The symptoms are largely the same and the antidote is the same, i.e., total avoidance of gluten for a life time.

[FlyingWotsitThingy]

5 minutes ago, trents said:

May we assume you have already been eating gluten free?

As with Cristiana, I am not an expert on genetics, celiac genetics or otherwise. So I won't attempt to analyze your genetic testing results or offer an opinion . . . except to say that my understanding is that not having either the DQ 2.5 or the DQ8 genetic markers does not rule out the possibility of developing celiac disease. I do know that those two gene markers were linked to Celiac disease through studies done with people of caucasian/European decent and since then there is evidence accumulating to the effect that other races may not show that same affiliation. I just think there is a lot we don't know about the genetics of celiac disease and that it may be a more complex and varied genetic phenomenon than originally thought.

The other thing I would offer is that if you have established the fact through experience that you cannot tolerate gluten then you may have NSGS (Non Celiac Gluten Sensitivity) rather than celiac disease. The symptoms are largely the same and the antidote is the same, i.e., total avoidance of gluten for a life time.

Hi Trents, thanks for replying. I’ve been avoiding gluten for the past ten years or so, though I’ll admit definitely not as strictly as I should with cross contamination etc if it is celiac. The person who originally tested me said I’d only need to give it up for a short time - maybe a couple of years, tops - but any time I’ve tried to reintroduce gluten I’ve felt terrible and had awful symptoms, some almost immediately, others appearing within a few days. I’m now wondering if that advice was irresponsible! 
 

I am of Caucasian European descent, if that has any impact…

[cristiana]

Hello again FlyingWotsitThingy

First things first.   I'm British, and Wotsits are cheese puff Cheeto type crisps here and I have to say that reading your name makes me smile each time I see it, with the thought of a Wotsit flying through the air!   Thank you for cheering me up!

But that aside...

Here in the UK I know a fair few coeliacs but none have been offered genetic testing.   I guess our National Health Service can't stretch to everything.   But L, like you, wonder which side of the family this condition comes from.  My paternal grandmother had some very strange symptoms suggestive of coeliac, although not digestive ones, and my mother's family have quite a few cases of diabetes type one.   My sister's boy was also diagnosed with diabetes type one a few years ago and his care plan includes being tested for coeliac every three years.  Despite all these things, I am the only known coeliac in the family so far - although I feel there may be one or two more who really ought to be tested but for some reason they (or their doctors) are resisting.

So the fact there are autoimmune conditions in your family is really interesting.  

We do have one or two people who contribute to this forum who are more up on these things so I am hoping will chime in if they see your post.   But I do think it is a great idea to get back to the lab and if possible, do get back to us with what they say.

I am sorry that you are struggling with eating gluten but I guess we are fortunate in that there is so much else available to us today to eat.   I have even found several supermarkets make their own brand Wotsit style crisp without gluten - definitely "one giant step for mankind"!😊

Edited August 6, 2021 by cristiana

[FlyingWotsitThingy]

3 hours ago, cristiana said:

Hello again FlyingWotsitThingy

First things first.   I'm British, and Wotsits are cheese puff Cheeto type crisps here and I have to say that reading your name makes me smile each time I see it, with the thought of a Wotsit flying through the air!   Thank you for cheering me up!

But that aside...

Here in the UK I know a fair few coeliacs but none have been offered genetic testing.   I guess our National Health Service can't stretch to everything.   But L, like you, wonder which side of the family this condition comes from.  My paternal grandmother had some very strange symptoms suggestive of coeliac, although not digestive ones, and my mother's family have quite a few cases of diabetes type one.   My sister's boy was also diagnosed with diabetes type one a few years ago and his care plan includes being tested for coeliac every three years.  Despite all these things, I am the only known coeliac in the family so far - although I feel there may be one or two more who really ought to be tested but for some reason they (or their doctors) are resisting.

So the fact there are autoimmune conditions in your family is really interesting.  

We do have one or two people who contribute to this forum who are more up on these things so I am hoping will chime in if they see your post.   But I do think it is a great idea to get back to the lab and if possible, do get back to us with what they say.

I am sorry that you are struggling with eating gluten but I guess we are fortunate in that there is so much else available to us today to eat.   I have even found several supermarkets make their own brand Wotsit style crisp without gluten - definitely "one giant step for mankind"!😊

I am also British 👋 so I know the crisps you mean. The name is actually in reference to a kids TV show from the 80s called 'The Trap Door' - the flyin' wotsit fingy is a little green bat thing! 

Interestingly, the Crohns and psoriasis are on opposite sides of the family, so it could be coming from both sides! I can understand the reluctance to be tested - I'm not exactly relishing the thought of an endoscopy, so that's why I'm trying to rule it out genetically first!

The gluten free offerings are definitely better now than they were when I first ditched the gluten ten years ago, so it's not all bad - just wish they could get the texture of the crumpets right!! 

[cristiana]

Re: Crumpets.  Oddly enough I actually prefer gluten-free crumpets, I find the normal variety have a very slight bitter taste to them, so "I'm awright Jack" on that one.   The thing I do miss however is doughnuts.  And, oddly, now when my family suggest a fast food meal I wish I could join them even though in the past I really didn't care for Macdonalds or KFC at all.

I googled the Wotsit TV programme - never heard of it, as I was a sixties baby so my staples were Swap Shop, Blue Peter and Trumpton.  It looks intriguing though!

Also, as I've just posted on another thread, re: endoscopies.  The British position on endoscopies may be changing somewhat.  It used to be considered the gold standard for testing but a few posts on this forum in recent months seem to indicate that if a blood test is convincing enough one may not be deemed necessary.  Of course, it may have had something to do with Covid and all the pressure that the NHS has been under, but it will be interesting to see what happens with that.

I do hope that you get the answers you are looking for from the lab, it would be interesting to hear what they say.

 

[deezer]

In short - yes - you have risk factors for developing Celiac disease.

What are you trying to find out?  What are your goals?

[Scott Adams]

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