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Joined: Oct 2008
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Magical_AS_Kicker
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Magical_AS_Kicker
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Sorry about the thread hijack SimplySouthern. I hope you can get to see a rheumatologist soon and start an appropriate treatment plan.

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Fifth_Degree_AS_Kicker
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Fifth_Degree_AS_Kicker
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JROC -- No worries -- more info is more to learn.

In response to the above, I am HLA+ and have the two as:

rs30187(C;C) www.snpedia.com/index.php/Rs30187%28C;C%29
rs27044(C;C) www.snpedia.com/index.php/Rs27044%28C;C%29

The above results seem odd with some of the other results like rs7743761(A;A). Mine as well started early but like many, it took over two decades to diagnose as the symptoms were more than axial.

Joined: Sep 2007
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Master_Sergeant_AS_Kicker
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Hi jroc and SimplySouthern,

I think you're reading that right jroc. Bad luck that you should have both the at-risk ERAP1 minor alleles for rs30187 and rs27044 - which is consistent with you being early onset mixed.
By contrast, you, SimplySouthern, have the major alleles for ERAP1 rs30187 and rs27044, that is, for these two SNPs you have the alleles that are not associated with AS.
As for rs7743761 - I think it's significance is lessened by the fact that it is on chromosome 6 - in or near HLA-B27.


Dx Oct 2006 B27+ undifferentiated spondlyarthropathy (uSpA) with mild sebhorrhoeic dermatitis and mild Inflammatory Bowel Disease (IBD) controlled by NSD since 2007.
Joined: Apr 2013
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Fifth_Degree_AS_Kicker
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Fifth_Degree_AS_Kicker
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Are you saying the significance is lessened (the rs30187 and rs27044) in my case because of the results being on the lower end? (sorry 4 nights of little to no sleep is making my logical side pretty lame).

On the flip side of the IL23R, of the seven, 6 are listed as Bad Reput and the other, neutral. I not sure if any of that has meaning. In your research, has anything crossed your path on that DavidP?

rs10889677(A;C)
rs11209026(G;G)
rs1004819(C;T)
rs11209032(A;G)
rs1495965(A;G)
rs1343151(C;C)
rs11465804(T;T)

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Master_Sergeant_AS_Kicker
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Hi SimplySouthern,

The study I referred to is one of the first to try and link variants of ERAP1 to the phenotype or clinical characteristics of AS patients.
Several SNPs of ERAP1 have been identified, namely, rs30187 (which means Lysine is replaced by Arginine at position 528, designated Lys528Arg); rs27044 (Gln730Glu); rs2287987 (Met349Val); rs10050860 (Asp75Asn) and rs17482078 (Arg725Gln). The authors restricted themselves to looking at rs30187 and rs27044 and whether or not these influenced Age of Onset (for a HLA-B27 positive patients) and axial Versus mixed pattern of disease for the early onset sub-group.
Even though those two ERAP1 variants are not contributing to your disease there are the other 3 ERAP1 variants to consider and as you point out the seven or so listed variants within the genetic code of the IL 23 Receptor protein.
IL23 is a very important cytokine (white cell chemical messenger) for AS patients. It is produced predominantly in the gut but unfortuneately there are a type of recently discovered lymphoid cells that are restricted to tendon and ligament attachment sites that are IL23R+ so they will respond to high levels of circulating IL23 by ramping up inflammation at those sites (rather than repairing any tendon micro tears as they are supposed to do).
Since as you have indicated you have six out of seven of the at-risk IL23R SNPs then perhaps for you the IL23/IL23R axis is more of a driver of disease than ERAP1 and may be you might be expected to have considerable issues peripherally and perhaps significant gut issues?


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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Master_Sergeant_AS_Kicker
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Hi SimplySouthern,
I went back to the first page and looked at some of your earlier posts. It clearly shows that you don't have any of the ERAP1 at-risk variants - so all good there.
But, as you pointed out you have 5 of the 7 IL23R at-risk SNPs - not good - so in conjunction with HLA-B27, IL23R must be driving your disease.
As for rs7743761 which you say Promethease locates onto DHFRP2. I think something is wrong there since a quick scan of the internet locates DHFRP2 onto chromosome 19 (I think). But this does not jell with the paper from 2010 that jroc referred to, that suggested rs7743761 is on chromosome 6 on, or near HLA-B27 - it may even be within HLAB27 - and that would lessen its significance.


Dx Oct 2006 B27+ undifferentiated spondlyarthropathy (uSpA) with mild sebhorrhoeic dermatitis and mild Inflammatory Bowel Disease (IBD) controlled by NSD since 2007.
Joined: Apr 2013
Posts: 372
Fifth_Degree_AS_Kicker
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Fifth_Degree_AS_Kicker
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I think that has been one of the hardest reasons to hold the diagnosis as when something has occurred in the peripheral areas, it has been dismissed as affiliated. I have had numerous issues in my hands, shoulders, legs and ankles (and brittleness of the spinal bones) so that would make sense. As far as gut, officially IBS and in the colon, other issues but when in flares, I really wasn't under a case that could diagnose it.

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Fifth_Degree_AS_Kicker
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Fifth_Degree_AS_Kicker
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I found this that supports Chromosome 6 for DHFRP2. Both 23andMe and Promethease has it under 6 as well. It looks like DHFRP1 is under 18 but I can't find anything connected to 19.

http://www.ncbi.nlm.nih.gov/pubmed/3341383


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Master_Sergeant_AS_Kicker
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Hi SimplySouthern,
I saw that you said nowhere did the results say you were HLA-B27 positive. Instead they gave just three SNPs within the HLA-B gene without comment.
HLA-B27 Human Leukocyte Antigen B27 is located on Chromosome 6.
HLA-B27 is one of 60 or so HLA-B alleles, and is a Major Histocompatibility Complex (MHC) Class I gene that encodes a peptide binding protein (in this case HLA-B27) that are expressed on all nucleated cells. The molecules consist of an α chain and β2microglobulin (not part of MHC) and present ligands (antigen fragments of 8-10 amino acids long, usually virally derived or ‘self’, but also can be derived from intracellular bacteria).
HLA-B27, like the all the HLA-B so called 'antigens' were originally defined serologically. That is, the serum of multi-parous women (multiple births) were run against panels of white cells from different people and eventually antiserum generated that could react with different groups of white cells so that the cells were designated as displaying surface markers HLA-B1 through to B60 (some are now redundant). We each have two HLA-B genes (one from each parent) so I might be HLA-B27/B14 for instance.
Since those days HLA typing has been refined and explained by different patterns of amino acids over stretches of hundreds of amino acids that comprise a single B type. This has led to further extensive subtyping within HLA-B27. This explains why a genome scan looking for SNPs will not be capable of readily identifying your 'B'status. Instead that is performed by a standard lab and reported as either HLA-B27 positive or HLA-B27 negative (eg. B14/B58)

The Major Histocompatibility Complex (MHC) is a large genomic region of 3.6Mb (3.6 million base pairs) situated on chromosome 6 containing 224 known genes, most having immune or related functions. The high allelic diversity in the MHC, particularly at HLA loci, is thought to provide a survival advantage due to the likelihood of heterozygosity increasing the range of antigens that can be presented.
The proteins encoded by the HLA genes are expressed on the surface of cells where they display both self antigens (short peptide fragments from the cell itself) or non self antigens (such as fragments of invading microorganisms) to a type of leukocyte or white blood cell called T-cells (lymphocytes) that have the capacity to kill or facilitate the killing of pathogens and infected or malfunctioning cells.


Dx Oct 2006 B27+ undifferentiated spondlyarthropathy (uSpA) with mild sebhorrhoeic dermatitis and mild Inflammatory Bowel Disease (IBD) controlled by NSD since 2007.
Joined: Apr 2013
Posts: 372
Fifth_Degree_AS_Kicker
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Fifth_Degree_AS_Kicker
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I'm HLA-B27+. I've been tested 4 times (I know why....because of doctors that wanted they own results over the course of years). Neither Promethease or 23andMe show the breakdown to that specification but list the subset genes of discussion here.

BTW - should I mention you are sooooo far advanced in research and interpretation of the papers than I.

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