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What Are The Exact N Genes Or Hla Type? Blood Test.


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#1 narcshark

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Posted 05 February 2010 - 01:37 AM

Hi Everyone!

I am wondering what exactly are the N genes or HLA codes for narcolepsy? I have read online that may people say they "have the gene" or "have all 3 genes" or some variation thereof. In my research, I have read that the following are all N genes:

HLA DR2
DQB1 *0602
DQA1 *0602
DQw1

I also read on a forum that the following genes are also N genes (although I haven't seen any scientific literature on these):
DQB1 *0301 Narcolepsy and Celiac
DRB1*04 Hypersomnolence
DQA1*0102
DQ6
DR15


So I am wondering, if anyone knows, are all of the above N genes? How does this all work?

#2 vidar

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Posted 09 February 2010 - 11:27 AM

Those are all HLA varients. Many of the ones you listed are MHC-II variants. To date I have seen no literature indicating a narcolepsy gene. I doubt one, or even several, truly exist for most patients. There have been two cases of mutations in the Orexin gene (A varient I think, there are both A and B proteins) that have been shown to be the causal effect of narcolepsy in those patients.

The reason for this is that HLAs genes on the immune system. Many HLA types have been associated with a predisposition to a disease but not the disease itself. There are also some cases where it may predispose to infection with a virus or other agent, or both infection or exposure to anything that can produce an immune response and an HLA type may interact to result in an autoimmunity.

A common saying is Genotype (your HLA for example) + Environment (disease exposure, toxins, lifestyle... everything else) = Phenotype (disease in this case).

I hope this helps and is not overly confusing.

#3 Marcianna

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Posted 09 February 2010 - 07:17 PM

Oh this is interesting.... I don't understand Vidar your are saying there isn't a specific set of N genes? Just predispositions? I wonder why they order blood test then if it is not something that is an accurate test? I remember having to be tested for the gene, to verify my DX. Was that just one more thing my old crazy doctor used to cushion the bill? (Man I couldn't stand that guy.) Glad you all brought this up. Good topic.

#4 vidar

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Posted 09 February 2010 - 08:53 PM

Your understanding of what I said was correct.

HLA testing is of some diagnostic value. Their are actually formulas used to determine the usefulness of a study or test in given population. From what I recall reading HLA testing is of "Moderate" value based on those formulas.

#5 Nyx

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Posted 09 February 2010 - 11:45 PM

Here's some more info from Stanford's Center for Narcolepsy (scroll down to the appropriate part of the FAQ on HLA). "The best HLA marker for narcolepsy is HLA-DQB1*0602.":

http://med.stanford....lepsy/faq1.html

For what it's worth, I heard in a talk about narcolepsy recently that that genetic marker cited above is only applicable to people with "sporadic" narcolepsy, and that as vidar posted, environment/exposure is definitely a significant part of it. Something like 75% (my best recollection) of identical twins do not both have narcolepsy when one of them has it, so it's clearly not due to genetics alone. Moreover, in the "familial" form, where many members of a family have narcolepsy, they supposedly test negative for that genetic marker.

And per Stanford's data, the genetic test cannot completely rule out or rule in narcolepsy. While the marker is present in 90% of people with narcolepsy and cataplexy, the marker is also found in 20% of the population generally, who do not have narcolepsy. And then the numbers get even messier when you get to narcolepsy without cataplexy. They did find, however, that there seems to be some relationship between having the marker and having deficient hypocretin in a CSF test, but that too isn't clear cut. So, the bottom line is that none of this is really necessary yet in clinical practice (i.e., for a diagnosis), but it still might be interesting to find out, and is definitely still in the research stages of development.

#6 merrymom1013

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Posted 10 February 2010 - 10:36 AM

As to why a doctor would include this testing for diagnosis... My daughter's initial onset of narcolepsy was unusual, complicated by other (also undiagnosed) health issues & she was young (10-11). A number of doctors were certain her problems were psychiatric. (Maybe because severe cataplexy is such a common feature of mental illness in children?? Not!) The presence of HLA-DQB1*0602 helped strengthen the certainty of the diagnosis. Cataplexy + a positive MSLT + HLA-DQB1*0602 makes a pretty definite statement & for her, eliminated the need for a confirming spinal tap. That much evidence also helps the insurance company be on board with approving the expensive drugs. Sounds like your doctor is trying to be thorough.

#7 Marcianna

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Posted 11 February 2010 - 02:37 PM

Blah.... Genetics. Sciency stuff. it might as well be math to me. Hahaha. Thank you all for clearing this up in my head. I made a t-shirt that says : "HLA-DQB1*0602 Whats your excuse? " I thought it would be fun. but Knowing how to explain it right would be useful....


Btw ... anyone able to figure out how to work the forum so that you can have normal size lettering and not teeny tiny? Drives me nuts....
Send me a PM if you know.. no reason to get off topic here.:D


#8 narcshark

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Posted 15 February 2010 - 10:05 PM

Thank you all for the helpful replies. I finally got my test back and I'm now more confused than ever...if anyone can offer any interpretation or thoughts, that would be most appreciated. The test that was ordered was called "HLA DRB1 & amp; DQB1 low resolution FH". If anyone can clarify the difference between the low resolution and the high resolution test, and if this is relevant, please let me know. It also says that Class I and Class II typing were obtained using molecular techniques.

My result showed "only one antigen/allele was detected for the HLA-DQB*1 loci of this patient. This most likely indicates homozygosity".
I know you might be thinking I should ask my doctor about these results (and I will) but frankly I don't get to see him again for several months, and I'd like to figure this out sooner rather than later. Thanks in advance for your help on this....I am so grateful for the input from those of you "in the know"....

#9 jenji

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Posted 15 February 2010 - 11:55 PM

Hiya Narkshark.

"I know you might be thinking that I should ask my doctor about these results."

Yes, that is what I'm thinking, however if you cannot see the doctor for several months why don't you just fax him/her your results so they're handy and he/she can tell you what they mean over the phone. Why wait and delay appropriate diagnosis and/or treatment?

Your test results read to be much more confusing than mine were; having said that, mine were still a bit confusing.

My diagnosis was made via MSLT, PSG, history (cataplexy etc) and finally HLA testing. I chose that in lieu of the spinal tap, as we had enough evidence already, but the genetic results were helpful for the insurance company, as well as my confidence in a correct diagnosis.

Mine read:

HLA Typing for Narcolepsy: Interpretation: The patient has the HLA haplotype associated with Narcolepsy (HLA-DR15, HLA-DQA1*0102, HLA-DQB1*0602).

HLA-DR15 POSITIVE
HLA-DQ6 POSITIVE
HLA-DRB1 11
HLA-DRB1 15
HLA-DQA1 0102
HLA-DQA1 0505
HLA-DQB1 0301
HLA-DQB1 0602

Frankly, now that I've taken another look at these results I'd like them better explained to me, especially since I have comorbid rheumatological conditions. I mean, I don't know if the 6 HLA's listed after the two positive mean I have them as well or what. I think it does because up top it says that I have HLA-DQB1* 0602, HLA-DQA1*0102 (which I realize are linked to HLA-DR15), however it doesn't say POSITIVE next to it down below. And so I'm thinking that I have the others, but that they're just not associated with N? I can hardly know for sure. And so, I looked up the phone number for the lab and I'm going to attempt to ask the PhD who read my results directly. My neurologist simply stated the obvious: POSITIVE for the first two that said POSITIVE, however it would appear that there are 3 total for N? I don't know, trying to understand this nonsense is ridiculous. You should definitely ask your doctor sooner rather than later.

And for the record, I fully understand the concept of predisposition. A person can test positive for a myriad of conditions and never develop the symptoms (that is, the disease) whatsoever; most immune disease is somehow triggered by environment et al. I believe my cocktail of illnesses were initially triggered by mononucleosis. I had mono in '87 and was considerably weaker than I had been before and then I had strep throat in '95, wherein I was never the same again; the trigger alarm really went off then; it was like an overnight thing. Fine one day, strep throat and never the same again the next.

Ugh. So sick of this nonsense.

Anyway, best of luck in getting your results read. Keep us posted!
jenji

#10 jenji

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Posted 22 February 2010 - 06:42 PM

Narcshark.

lol Okay, you should totally market those pharmacy cards! My current pharmacy is fantastic, however I know what you're talking about, as I've been given the eye in the past. Picking up uppers and downers at the same time? You'd think I was the reincarnation of Judy Garland looking for reds and blues in a sequined red dress. (RIP judy).

Anyway, good luck with your new HLA testing. I've been gluten-free since May last year and it's really not all that bad once you get on a schedule and get used to it. The thing that really helps me is that most sweets are still okay, as I have a major sweet tooth. Not baked sweets per se, but chocolate and candies are mostly okay. There are some great online sites that list all the safe products/brands/restaurants for those who are trying to avoid gluten. Every once in awhile I have very vivid dreams about cake- proper cake. Other than that, the GF plan is pretty doable.

Hopefully your condition can be improved via dietary changes. I'm simply on it because it has been suggested that going gluten-free is helpful for those with autoimmune conditions and since I have a few, well there you have it. I was never tested for celiac, although I wish I had done so before I went GF. There's no point in getting tested now, as it's been out of my body for so long. Besides, I have the genetic positive N result, so what's the major difference? I could be tired via either condition. I can say that I no longer have what was deemed years ago to be eczema, nor do I ever, ever have gas or bloating. Also, my visits to the bathroom are near regular (TMI?), wherein they used to be few and far between. I went from 1-2x's/every two weeks to almost everyday. Is this TMI? Apologies.

Anyway, good luck! And get on marketing those cards! They could apply to so many conditions.

jenji

#11 sleepless sleeper

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Posted 23 February 2010 - 01:40 AM

I had mono in '87 and was considerably weaker than I had been before and then I had strep throat in '95, wherein I was never the same again; the trigger alarm really went off then; it was like an overnight thing. Fine one day, strep throat and never the same again the next.

recently a member on here was discussing strep in another forum. i'm so tired right now and can't focus to discuss this appropriately. i left him a message to see if he was interested in discussing the topic here. apparently strep does more than many thought it did. i've had it multiple times. he's had it. his sis has N, and she had strep, and so on. then again, strep is quite common.

hope all is well.

#12 BrainScatters

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Posted 10 March 2010 - 03:27 PM

Just wanted to jump in on the "I hate pharmacists" note and put my order in for a card. I'm so sick of getting crap from pharmacists who think that because they count out pills for people (yes, I know there's more to it) that they can offer medical advice and are part of the medical profession. I was going on a trip to Austin and went to get my Nuvigil refilled a couple of days before I ran out so I wouldn't run out on the trip. It wasn't any kind of too early by the legal terms, but they wouldn't do it until like the day before it ran out. I asked them what the deal was and mentioned I was well past the legal waiting, blah blah and they said it's just arbitrary. They do it on a case by case basis.

On an up note I was so furious it woke me right up for like 3 hours. On a down note I had to reschedule my trip because they arbitrarily try to pick out the junky. Now, I don't have a lot of experience with narco meds yet, but I'm just guessing that Nuvigil isn't exactly at the top of the list for people to abuse. Maybe it does something for "normal" people, but if I was looking for something recreational, the amount I spend on this stuff would support a pretty healthy illegal drug habit.

Anyway, sorry to rant. :)

#13 narcshark

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Posted 14 May 2010 - 01:51 AM

Okay, so here it is....everything you always wanted to know about HLA typing and N, but were afraid to ask, from a patient's perspective....please note I am not an MD, and reserve the right to remain perpetually confused about this topic. Posted Image

A few thoughts from my humble research....first, if you are going to get the HLA typing done, be sure that your doc orders the high resolution test. If the low resolution test is done, the results will only include the first two numbers of the code, rather than the 4 that you are looking for, so you will not have enough information to conclude whether you have the N alleles or not. For example, you might find out that you have DQB1*06, but you won't know if it is the magic DQB1*0602 or something else....so ask for the high resolution test. Also, if they do the "antigen" version of the low level test, you will get even less info....so you might find out (like I did) that you have DQB1, but not know the numerical part at all...again, leaving you in a state of total confusion.

As to what HLA patterns mean what, as far as narcolepsy goes, I found this fabulous article from 2001 by Mignot and colleagues. I am posting the link here: http://med.stanford....cles/ajhg68.pdf. If you have any question about what your exact HLA type means, it is likely addressed in that article. Also, if you are having any problems with insomnia, that article may also come in handy Posted Image But seriously, it seems to be thorough, to say the least.

Some other papers that contain some good information are these (they are not about narcolepsy, but include detailed information that is helpful in understanding HLA typing). http://www.seopf.org/PTRMar2008.pdf, and http://www.unos.org/.../hla_typing.pdf.

So, I think that I now have my answer to the original question that started this post....I hope this helps others too....

#14 narcshark

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Posted 17 May 2010 - 07:31 PM

There is a chart located in the article at http://www.chemie.de/lexikon/e/HLA-DQ/ that depicts the top 25 most common serotypes for Caucasians. Sorry I couldn't be more inclusive...this is the best chart I could find. This chart suggests that the N serotype (a variant of DQ6) is the most common, at 14.2%.

For those of you who have had your HLA typing done, you can use the chart in the article to look up your serotype, then go across the chart to take a look at your haplotype (not all of them are shown, only the 25 most common). This chart allowed me to understand my results much better. My understanding from other research is that the strongest N serotype is called DQ6.2...

This chart came from an article located at

http://www.chemie.de/lexikon/e/HLA-DQ/

I tried to embed the chart in this response but it didn't work.