Monday, April 2, 2012

I have HLA-B*1502 (23andme genetic testing)?

Update:
After some more research, I actually believe that 23andme does not call this SNP properly and/or it does not actually correspond with HLA-B 1502. I guess I'd have to get tested elsewhere to know for sure, (but I have no intentions of doing that).

The reason why I say this is because at one point in time Gedmatch.com had a rareSNP finder and this one did not come up as "rare" for me. I believe it showed frequencies all the way up to 20%. If more than 20% of people on Gedmatch shares this genotype, then it is quite common and could not possibly be accurate.

So I just wanted to throw that out there. All of my East Asian fell off of my Ancestry Composition when they updated it. So personally I think this SNP is not accurate and I would not be worried. If you are worried, then get tested at a lab for HLA-B 1502.
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I kind of left all of you hanging there with my last post. I decided instead of taking another week to get all of my research and thoughts together, I'd just let you know what I found out with this 1 particular genotype.

Genetics is very confusing and I don't even partially understand it, but as you all should know, there are very important markers within our genome for our immune system. These are called HLA or human leukocyte antigen. These are located on Chromosome 6 and are responsible for the way our immune system responds.

When I ordered 23andme genetic testing, I was looking for anything at all that might give me some insight into my health. Well I think as far as discoveries go, I probably hit the jackpot. When someone opens up their genetic information, most people want to be warned about potentially harmful conditions or to alert them of some sort of disease they are carry etc.

After I looked in the initial reports provided by 23andme, I wanted to go even further. I downloaded my genetic raw data to my computer and loaded it into a program called Promethease. This program is free (or you can pay a cheap $2 to speed up the test) and it will alert you to any mutations or genotypes they feel are important.

In the "Bad section" I found something that had an extremely low frequency, high magnitude and seemed like it should have had a huge sign that said, HOLY SH*T READ ME, but it did not. Thankfully I was paying very close attention...

According to this test I carry what is called HLA-B*1502. People with this allele have a 1000 fold increased risk of developing Stevens Johnson Syndrome (remember me talking about this while chelating?) when taking carbamazepine, phenytoin and fosphenytoin. These are anti-epileptics drugs, but they also have other uses. Here's where it gets really weird though. If you look up any information on this it only talks about  this occurring in Asians. Well I'm not Asian, so I was pretty perplexed by this. The frequency for this allele to occur in a Caucasian is 0.0-0.1%. Yes that is 0.1%.

You can watch a short video from the FDA alerting people of this.


On 23andme I made a thread about my finding and some were suggesting that since I wasn't an Asian that this did not apply to me. I challenged this theory. No Caucasians were ever seen with this allele in any literature (Study 1, Study 2, Study 3 or Study 4) Therefore one cannot make the assumption that it would be safe to take these drugs. The only thing these studies were trying to show were that there are other HLA-B genotypes which have a higher prevalence in the Caucasian population which were causing CBZ-SJS.

Out of curiosity, I emailed one of the authors of the study and asked him if me (a Caucasian) would have the same risk as an Asian and he said Yes. I should avoid both carbamazepine and phenytoin.

Are there any other Caucasians out there with HLA-B*1502? Part of me wants to get this checked through Quest Diagnostic or Lab Corp to confirm I do in fact have this...When you come across something like this, I need further proof.  There is an entry in snpedia that testing for this may not be accurate because it is phased data.

The defining SNP's (said "snips") are:
rs3909184 GG
rs2844682 AA

The first one GG is common. It is the second one at AA that is rare in Europeans.  You need to have both of these in order to have HLA-B*1502. This association with HLA-B*1502, CBZ and Stevens Johnson Syndrome is well documented. If for some reason I would have ever needed an anti-epileptic, I never would have refused either of these two drugs.

Stevens Johnson Syndrome is serious business and it either kills you or leaves you in so much pain with health problems for the rest of your life. Some of the saddest videos I've ever seen on Youtube are of those people with Stevens Johnson Syndrome. They will break your heart...

5 comments:

Harry said...

Your symptoms sound very much life Pyroluria, have you ever been tested?

I suffered from adrenal fatigue and many, many other symptoms until I discovered Pyroluria. I encourage you to do a few Internet searches on Pyroluria if you haven't heard of the disease before.

I blog about life with Pyroluria at http://pyrolurialife.com

xythe13 said...

Thank you for this blog post, I ran across it when searching for information about Tegretol. I've had the 23andMe analysis done, I'm going to get the Promethease report also.

Kuenstle said...

Me! I am Caucasian, 99.9% European (and all western at that) on 23andme and I also did the promethease and had the same marker for HLA-B*1502. I thought it was really surprising and came across your blog, trying to google Caucasian HLA-B. So I guess there are two of us now...

My 23andme though also gave me a speculative and standard .1% East Asian (a total surprise for blonde, blue eyed, Western European). And said my maternal haplotype is H8 (which is also Asian), so maybe the FDA is right, and we are in fact not quite as European as we think...

Anyway, with this apparently non Caucasian marker and being Caucasian in common, I wonder if we might share a common ancestor? If you want I'm game to compare snps on 23andme, because it's definitely odd to find I'm one of what seems to be just two, with this weird genoset

Dana said...

Hey Kuenstle,
After some more research, I actually believe that 23andme does not call this SNP properly and/or it does not actually correspond with HLA-B 1502. I guess I'd have to get tested elsewhere to know for sure. If you ever have that done, I'd be curious to see if it matches up.

The reason why I say this is because when Gedmatch.com was still up, they had a rareSNP finder and this one did not come up as "rare" for me. I believe it showed frequencies all the way up to 20%. If more than 20% has this, then something is wrong.

So I just wanted to throw that out there. All of my East Asian fell off of AC when it changed a few months ago.

Mama D said...

So...ditto. I can go back many generations with only Western European ancestry and have HLA-B*1502. This as I start on not one, but TWO medications warning against Stevens-Johnson Syndrome. Lovely.