Kickas.org Forums Ankylosing Spondylitis General Discussion #1 AS Web Support Group AS in Men & Women - Interesting Article

Found this today when I was searching something completely different. Thought it was intriguing.

Genetic Differences in Men & Women with AS

Happy reading!

Hugs,

Thanks for the post Kat--what I can understand of that article, it looks like it is going to be very interesting (only made it through the first part so far). I have to say, the first half of the first sentence almost made me stop reading, as I did not understand a word of it! ("The ank (progressive ankylosis) mutant mouse, which has a nonsense mutation in exon 12 of the inorganic pyrophosphate regulator gene (ank), . . . ") Well, let me rephrase that: I understood what individual words meant, such as 'nonsense' and 'mutant,' but I sure as heck didn't understand what they meant in the order they were used!!!!

A couple things struck me as particularly interesting right away. They were:

1) Early in the article, it says that "The prevalence of AS is 2.5 times higher in men than in women " So, roughly a ratio of 2.5 men for every 1 woman. A bit further down, as they describe the group of families they assembled for the study, they say that

"The study group comprised 201 Caucasian AS families (a total of 226 nuclear families; Tables 1 and 2). This group was recruited from the Toronto Western Spondylitis Clinic (23 families) and from other sites in the North American Spondylitis Consortium (178 families). All patients met modified New York criteria for the diagnosis of AS [19], which include radiographic evidence of sacroiliitis. Of the affected and unaffected individuals, 60% and 47% were men, respectively."

Hmmm....so if 60 percent of the affected individuals in this study were men, let's do the math there. While I have admitted many times that I am no mathematical genius (hence the editing career), I think even I can handle that simple ratio: If we had 100 affected men and women, 60 of them would be men, 40 would be women. Well gee, that sounds like a 3-to-2 ration, not 2.5-to-1 (or, 5-to-2). I realize the size of the group they used is likely not large enough to draw statistical conclusions on the rate of the occurrence in the population in general, but dang it, it is yet another piece of evidence that shows that the 2.5-to-1 number is probably no longer accurate (if it ever was). That ration converts VERY roughly to 7 out of 10 people; in other words, a ratio that very much supports doctors when they tell women "Don't worry, women almost never get AS." Uh-huh. Ok. To me, based on what we see here in KA, a 3-to-2 ratio sounds much closer to being an accurate estimate of men with AS vs. women. Please, anyone who is laughing at my math right now, most definitely correct me, as I could definitely be wrong on this!

2) This is the other sentence that caught my eye (well, start of a sentence--I did not copy the entire sentence, only this part, but the latter does not contradict this part in any way).

"Gender also has a significant impact on heritability in AS. AS has a higher prevalence in the offspring of women than men with AS, . . . . "

When I think back about the parents who have posted in here saying that their children also have AS, the overwhelming majority that I remember were women. I do remember a couple men saying one or more of their children had AS, but not many at all. Obviously, something like this--ie, number of women vs. men who posted in KA and said their children had AS--is nothing more than anecdotal evidence with no scientific validity, but it is interesting that it does seem to back up what they are saying in this paper. Of course, if I'm saying above that I have a hard time believing one number they cite (the 2.5-to-1 men-to-women ratio), then I have to view any other numbers with a grain of salt, as I can't just pick and choose. Or can I? The former number was cited from a time-honored (time-disgraced?) AS paper written back in 1985. The numbers concerning gender and prevelance in children, on the other hand, is at least a bit more recent, as the authors cite studies from 1999 and 2003. Perhaps that second number IS more reliable than the first, then. Can't be certain without digging out the original papers and seeing how the studies performed to provide the data for those papers were conducted, so I'll just leave things this way: It was an interesting point that, if true, has been anecdotally supported here in KA.

And that's enough of using my brain for one day. lol

Brad.

See, I just don't go into trying to figure out the ratios. Numbers and equations tend to make my brain twitch, which usually ends up with a physical twitch under my eye. At least 2.5:1 is waaaaay more accurate than 10:1, which was common belief even just 7 years ago when I was diagnosed.

What I found very interesting about this was the genetic differences in men and women with AS. That -5 and -3 whachamacallit thingmee that may account for the differences in disease progression between men and women.

Many hugs,

Brad,
Regarding your ratios in #1-You are right; the male to female ratio for the participants in this particular study is greater than 2.5:1. However, one can't necessarily extrapolate from the male to female ratio in this study to the ratio in the general population. How were the participants chosen for this study? Perhaps they were recruited in a way that was more likely to attract women than men. If the recruitment wasn't completely random (and it's very difficult to make it so), then the results may be skewed.

That doesn't mean I don't believe that women get AS. For heaven's sake, I think I have AS myself. And I'm glad AS is becoming more readily recognized and diagnosed in women so that women can get appropriate treatment.

Karen

I can't seem to pull up this article. Maybe it has something to do with my slow dialup.

Well, I can't answer to how the patients for the study were chosen, but I can say that many of them would have been the doctors' own patients.

That said, am I the only one who finds it exciting that somebody, somewhere, has bothered to try to figure out what's going on with the gender-based differences in this disease? Am I the only one who gets that maybe the reason for the lag in diagnosis in women could be based in this variance:

In this study of the association of ANKH genetic markers with AS, including 201 AS multiplex families, we found that ANKH variants located in two different regions of the ANKH gene were associated with AS. A more striking finding was that the genetic association for men and women with AS differed. In men, AS was associated with genetic markers at the 3' end of the ANKH gene, whereas in women AS appeared to be associated with genetic markers at the 5' end of the ANKH gene. As expected, when the genders of AS patients were analyzed separately, we observed more than one SNP in each region (within the same haplotype block) showing significant association with AS. Haplotype analyses appeared to confirm the results of the single-marker tests (FBAT analyses), indicating that the predisposing polymorphism(s) for men with AS probably lies at the 3' end of the ANKH gene, whereas those for affected women are probably at the 5' end of the gene. After Bonferroni correction for the number of haplotypes and models, the haplotype combination of rs26307 [C] and rs27356 [C] was significantly associated with men with AS; and the haplotype combination of rs28006 [C] and rs25957 [C] was significantly associated with women with AS. However, in both cases, the significance level was modest. We attribute this to the fact that we have not identified the aetiological variants in the men/women with AS. Despite the modest P values (which are a function of sample size), the calculated 'odds ratios' for increased risk (which provide estimates of the magnitude of the effect) were close to 2 for the transmission of rs26307 [C] rs27356 [C] to affected men, and close to 3 for the transmission of rs28006 [C] rs25957 [C] to affected women in the subset of families with affected individuals of both genders.

A test of interaction identified the region that was associated in men with AS (rs26307) as showing a difference in the strength of the association by gender. The region associated with AS in women only showed significance of the test of interaction among the subset of families with affected individuals of both genders. Our current efforts are to identify and analyze more common SNPs in these two regions, ultimately finding the predisposing polymorphisms in men and women.

Sorry if I sound frustrated, but the ratio of men:women is not the point of this article and it frustrates the crap out of me that women and the progression of AS in women are constantly (apparently) being ignored. Does this genetic difference make a difference? I don't know, but it is proof positive (to me) that there is a difference. And if more GPs and PCPs and rheumies knew about these things, if researchers bothered to do studies on women, maybe women like our Karen and Sue wouldn't be lost in diagnosis limbo. It has to start somewhere and this seems a pretty good start - figuring out that there is a genetic difference in where the disease sits in men and women (if that's what this article indeed says - my brain twitch activates automatically after a point). Why does it appear that AS is severe in different ways in both genders? Why does it appear that severe kyphosis is more common in men? Why does it appear that fusing doesn't occur in women until later in life? I don't know about anyone else, but I want to know these things and this is the first time I've seen anything beyond Dr. Monika Østensen and Dr. Harald Østensen's research of over 10 years ago that even talks about women with AS in a research capacity. One other article I've found (one dating back to 1959) acknowledge that women get it more frequently than was generally thought and noted differences in progression, but again, nobody actually bothered to look into the whys, the wherefors, and the hows. And nobody was actually listening in this particular case either, because this doctor felt in 1956 (the year the research was done) that the ratio was closer to 5:1 and for another 40 odd years, the mainstream medical community still believed the 10:1 crap.

By the way, for our moms to be out there, here's an article on their research: Ankylosing Spondylitis: The Female Aspect

OK, I'm going to get off my soapbox now. grumble grumble grouch. I need more coffee.

Warm hugs,

Hey Cindy, try this link from PubMed Central

Hugs,

No, Kat, you aren't the only one who is excited by the fact that researchers are FINALLY recognizing that AS presents differently in women, leading to underdiagnosis and undertreatment. It's marvelous news to finally see some research action in this area.

And you aren't the only one who has had the crap frustrated out of her. When I suggested to my PCP that I might have AS, do you know what she said to me? She said, "I don't think you have AS, Karen. It's primarily a male disease and I've never seen a women with AS." Ack! I set her straight very quickly and provided her with research material to back up what I was saying. The good news is that she listened to me with an open mind, looked at what I gave her and revised her thinking accordingly. One doctor at a time, we can change the world!

It's an exciting article, one that I hope will be read by many other doctors and researcher and one that I hope will stimulate further research in this area for the good of all of us. And maybe some day, the doctors will know and we won't have to correct them.

My reply regarding the ratios was somewhat nitpicky, but the scientist in me saw the error in thinking and wanted to correct the a possible misinterpretation of the data, leading to a conclusion not necessarily backed up by the data presented.

Karen

OK, I'm in a brain fog today and can't read that at all. Too many big words, and like Brad I know what the words mean, but not how they are strung together!

I'd just like to say that my rhuemy kicks butt!! After a year of being diagnosed with fibro I told him when my fibro feels fine my lower back still really hurts. He looked me over sent me for an x-ray and then for an MRI and blood work. Even though the blood work came back neg and my sed rate is low he still diagnosed me with AS. Mostly spond, but he thinks it's AS. He said the MRI results are looking very much like AS, but it's one piece of a 7 piece puzzle. But since I'm a lady he thinks it's just different for me!! I was so happy he thinks this way! He said many women have lower sed rates, neg blood work and have problems in other areas like my knees and hips and shoulders that give me problems.

If this article is talking about how women are ignored because we're women and that we need to get better about it, I think more drs need to talk to mine!

Hey Kat, isn't Inman your doc???