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Joined: Sep 2001
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Platinum_AS_Kicker
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Yes fascinating, I don't understand a bit of it but fascinating neverless.
Glad there are much smarter people than I researching this stuffs. laugh2



This bunny Kicks AS !
Joined: Apr 2013
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Fifth_Degree_AS_Kicker
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Fifth_Degree_AS_Kicker
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I have to agree with Stormy and snowshoe....it's well above my head but I'm grateful someone has the knowhow to dissect some of these publications.

Another one I saw today that I found interesting but for those with the 3 genes (HLA-B27, EARP1 and IL23R) holds a one and four chance of developing AS. I don't know how credible it is (in light of the advertising at the bottom of the page).


http://www.sciencecodex.com/major_geneti..._treatment_hope

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Master_Sergeant_AS_Kicker
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Thanks jroc and Simply Southern, you inspired me to pay the $280 (Australian, including post) to get tested by 23andme.

Basically my results are identical to Simply Southern, that is, I knew already that I was HLA-B27+, and the genetic test showed that I carried no ‘at risk’ ERAP1 alleles, but carried 6 out of 8 IL23R variants with bad repute.

According to me (and no one else), and according to the ‘ubiquitous pathogen exposure hypothesis’, HLA-B27+ individuals who also carry ‘at risk’ alleles of ERAP1, will develop a spondyloarthropathy when activated gut dendritic cells stimulate gut-mucosal memory T cells to be polarised toward a Th17 phenotype. Elevated levels of circulating IL23 will drive the disease processes such that those individuals who also carry ‘at risk’ alleles of IL23R will also suffer significant peripheral enthesitis and IBD / Crohns-like symptoms on top of the axial aspects of AS.

Individuals who are B27+ and have ‘at risk’ ERAP1 drivers, but not IL23R risk alleles might be expected to present as classic early onset AS but without significant gut or peripheral symptoms? Such cases might feel they are unaffected by diet?

In the case of someone like me, with B27 and IL23 drivers, but without ‘risk’ ERAP1 alleles, they might be expected to suffer gut and peripheral symptoms with lesser axial symptoms (no fusion).

I’d encourage more KickAS’ers to get tested.
Regards David.


Dx Oct 2006 B27+ undifferentiated spondlyarthropathy (uSpA) with mild sebhorrhoeic dermatitis and mild Inflammatory Bowel Disease (IBD) controlled by NSD since 2007.
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Magical_AS_Kicker
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That's cool David, thanks for sharing. That's an interesting hypothesis.

Did 23andMe provide any health related info or did you have to get that by running the raw data through Promethease? My understanding was that since the FDA shut them down a while back they are no longer allowed to offer any health interpretations of results, just ancestry information.

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Master_Sergeant_AS_Kicker
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Hi jroc,

23andMe provide only the raw SNP data, and as you say ancestral paternal and maternal (mitochondrial) DNA typing.

As you would know, you have to pay an additional $5 to run the data through Promethease. You retain access to Promethease's results for 45 days only.

There is some value in rerunning your results through Promethease a year or 2 down the track as the information attached to each SNP might in the future change depending on scientific advances.

I'm still confused about the DHFRP2 gene SNP on Chromosome 6 which like you gives a 4.6X increased risk of AS for me - I still think that this is probably due to linkage disequilibrium with HLA-B27 ?

Regards David


Dx Oct 2006 B27+ undifferentiated spondlyarthropathy (uSpA) with mild sebhorrhoeic dermatitis and mild Inflammatory Bowel Disease (IBD) controlled by NSD since 2007.
Joined: Oct 2008
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Magical_AS_Kicker
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Ah ok, that's what I thought. I was just wondering as 23andMe has a detailed report on Crohn's risk with 12 different SNPs in their Health Risks section.



Promethease will no doubt cover all those same SNPs. It's a shame they had to shut down the health risks reporting in 23andMe as I quite liked the way they did it with showing the general population risk, your risk based on your SNPs, the relative risk factor, and info on the role of genetics vs environment for that disease, links to studies etc.

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Fifth_Degree_AS_Kicker
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DavidP

I had read the same hypothesis about the two (ERAP1 and IL23R). I'm glad you are encouraging others to do the tests as well as I honestly think there is something to this Axial (ERAP1) versus more Peripheral (IR23R) involvement and wonder about others AND, how it in massive results, it could help many seeking the proper care.

If this is something found with substance, it would certainly turn my life around as for 25 years I have been told all my issues have no bearing on AS (or SpA).

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Fifth_Degree_AS_Kicker
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jroc,

Earlier this year, the FDA did ease up on the restrictions however, it doesn't seem as if they have yet changed that (since DavidP and I both got just the raw data).


http://www.nytimes.com/2015/02/20/business/fda-eases-access-to-dna-tests-of-rare-disorders.html?_r=0

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Master_Sergeant_AS_Kicker
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Hi Simply Southern,

In the future, knowing your ERAP1 or IL23R SNPs might be helpful in the choice of drug therapy.

I found a paper in the Romanian Journal of Rheumatology for 2015 that addresses the impact of IL23R in AS - it's worth a read.

https://www.kickas.org/ubbthreads/ubbthre...ded&fpart=1

Regards David.


Dx Oct 2006 B27+ undifferentiated spondlyarthropathy (uSpA) with mild sebhorrhoeic dermatitis and mild Inflammatory Bowel Disease (IBD) controlled by NSD since 2007.
Joined: Sep 2007
Posts: 608
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Dx Oct 2006 B27+ undifferentiated spondlyarthropathy (uSpA) with mild sebhorrhoeic dermatitis and mild Inflammatory Bowel Disease (IBD) controlled by NSD since 2007.
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