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Thread: Gene Associated With Adolescent Idiopathic Scoliosis Identified

  1. #181
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    Oh, here's something interesting.

    When I was spurred to read the multiple sclerosis stuff (to see if there were other diseases where an infectious+environment+genetic etiology was suggested), I noticed that they'd done some epidemiological research that showed that it was affected by latitude. Those who got more sunlight, had less MS.

    Oh, I thought, wouldn't the same thing maybe be possible in scoliosis, given the whole low bone density thing? (Does everybody already know this? Well, it came as a surprise to me). Anyway, while digging around in the SOSORT articles I ran across an interesting review, and it said what I'd been unable to find. Yes, there is some thought that scoliosis is affected by latitude.

    Here's the snippet:

    "Epidemiology
    In approximately 20% of cases, scoliosis is secondary to another pathological process. The remaining 80% are cases of idiopathic scoliosis. Adolescent idiopathic scoliosis (AIS) with a Cobb angle above 10 occurs in the general population in a wide range from 0.93 to 12% [21-38]: two to three percent is the value the most often found in the literature, and it has been suggested that epidemiology changes according to latitude [24,39]."

    Article here:

    http://www.scoliosisjournal.com/content/7/1/3

  2. #182
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    By the way, I thought those last four threads you started recently in the research section were quite good. Interesting and helpful in my opinion anyway.
    Sharon, mother of identical twin girls with scoliosis

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  3. #183
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    Not about scoliosis, but very cool, nonetheless

    http://www.uofmhealth.org/news/archi...c7Wbs.facebook

    Special bioabsorbable medical device fashioned with a 3D printer saves a baby's life.

  4. #184
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    Back to the latitude study, two charts from the report itself.

    The first shows the prevalence of AIS charted by latitude:

    http://www.scoliosisjournal.com/content/1/1/9/figure/F1

    and the second the age at menarch, also charted by latitude (the curve in the top chart is due to the following: "Age at menarche shows a decreasing trend as the geographic latitude approaches approximately the 25–30 degrees and then increases again toward 0 degrees (near the equator) ")

    http://www.scoliosisjournal.com/content/1/1/9/figure/F2

    So, unlike what I was thinking, that it was about light and bone density, this author is suggesting another mechanism. And, hey, it's melatonin.

    "A hypothesis
    It has been assumed that there are two types of pathogenetic factors for AIS, the initiating and those that cause progression. Initiating factors that can meaningfully be distinguished from progressing factors would eventually faint or disappear, while progressive factors, which are generally thought to be a mechanical process, are associating with curve magnitude [111].

    A possible preservation of high levels of melatonin secretion during the pre-menarcheal period in scoliotic girls due to light insufficiency in northern countries is associated with delay of the age at menarche. These high levels of melatonin are possibly identifiable before presentation of AIS, but would not be apparent at the time of clinical presentation of AIS in the vast majority of cases. The pre-menarcheal elevated levels of melatonin could be considered as a possible initiating factor of idiopathic scoliosis and it does not correlate with the severity and the site of the curve. It alters growth by lengthening the period of spine vulnerability while other pre-existing or aetiological factors are contributing to the development of AIS. Longitudinal studies on melatonin secretion in pre-pubertal girls that are at risk to develop AIS (i.e. with trunk asymmetry but no radiographic evidence of AIS) could be undertaken in order to test this hypothesis."

    [Added: But, from another study on scoliosis and latitude: "A positive association between prevalence of AIS and geographic latitude is reported only for girls in the present study. Prevalence of AIS in boys is not associated significantly with geographic latitude. This differing significant association implicates the possible role of environmental factors in the pathogenesis of AIS that may act in a different way between boys and girls."]
    Last edited by hdugger; 05-23-2013 at 09:29 AM.

  5. #185
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    That, in fact, is very interesting. Dingo found a paper that implicates melatonin with AIS. I don't have time to look for it, but the gist of that paper was that there was a disruption in the melatonin pathway (endocrine stuff). I've always held this one in the back of my mind as one of the most important finds. In that study, if I remember correctly, the melatonin was being processed insufficiently or inadequately, therefore increasing intake of melatonin would not help (since the body wasn't metabolizing it properly). That indicated, at least in my mind, that there was a decreased amount of normal melatonin available, not an increase. This could be a genetic factor, since genetic diseases often disrupt natural pathways or cause malformed gene products (proteins).

    I had late onset menarche, too. I lived in a northern latitude until I was 9-1/2 years old (Washington State), then moved to a lower latitude state for the remainder of my childhood (Arizona). This leads me to muse about whether or not the "trigger" could be location. I would be curious to know how prevalent scoliosis is in children born and raised in Alaska vs. any southern state or region. When I find time, I'll try to see if I can find this information. Anyone else who has some free time is welcome to beat me to the punch. Although, most of the research that I've read seems to suggest that the incidence of AIS, JIS, IIS is pretty stable worldwide. It's still worth looking into. South of the equator, it would be just the opposite trend, if this has any merit.
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  6. #186
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    It's in the first chart in the post above - prevalence of AIS by latitude. I believe if you go directly to the study, it lists all of the studies it draws that graph from, where they're located and the prevalence in that location. Looking at the prevalence rate in the studies, I couldn't quite see the line (although Sweden was off the charts at 12%), but I believe them that they ended up with the line in the graph - it's just that the numbers bounce around a lot.

    In MS, I think they can really chart it. People who live all their lives at northern latitudes have the highest prevalence, people who live all their lives at the lowest the least, and people who move between the two are somewhere in between.

  7. #187
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    Quote Originally Posted by hdugger View Post
    It's in the first chart in the post above - prevalence of AIS by latitude. I believe if you go directly to the study, it lists all of the studies it draws that graph from, where they're located and the prevalence in that location. Looking at the prevalence rate in the studies, I couldn't quite see the line (although Sweden was off the charts at 12%), but I believe them that they ended up with the line in the graph - it's just that the numbers bounce around a lot.

    In MS, I think they can really chart it. People who live all their lives at northern latitudes have the highest prevalence, people who live all their lives at the lowest the least, and people who move between the two are somewhere in between.
    Great, I will look at it when I have a chance. I have to go offline for now. Thanks!
    Be happy!
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  8. #188
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    But, if it is melatonin, why is it not affecting boys in the same way (second study)?

    In Epidemiology, there's a seminal study by Snow where he figures out what's causing the cholera epidemic. It's a thing of beauty, which is why all students learn about it. It's this map of the streets of London, with all of the cases of cholera as dots on the map. And you can just see these little clusters. And he's racking his brain to try to figure out what's happening more at the places with all the dots and less everywhere else. And then, at one point, he just gets it and sees that it's coming out in waves surrounding the public water pump on Broad street.

    Here's a blog post with an image of the map. The cases are clustered in black, all of the pumps are circled in blue, and you can just *see* all of the cases in one big cluster around that one pump on Broad street.

    http://microwavenews.com/news-center...m-appreciation

    Snow shut down that pump, and the epidemic stopped.

    In my dream world, we have a Broad street pump, or, at least, a bunch of different Broad street pumps. And, if you can't shut them down, you can at least lessen the flow.

  9. #189
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    "IF" idiopathic scoliosis turns out to be related to a melatonin pathway (it was just a paper that dingo posted that also implicated another pathway), we have to remember that this is an endocrine issue. We seem to think, or at least I did, that "endocrine" meant the hormones we are most familiar with such as the sex hormones, ex: Estrogen, Progesterone, Testosterone, etc. However, endocrinology really looks at how one chemical in the body affects how cells respond and "communicate" with each other in order to trigger a cascade of events in the body. An example of this would be how hormones produced in the thyroid gland can affect heart function, hair growth, and bone density among other things. They all seem unrelated, but they're not.

    Now let's get back to the gender differences. Women have a hormone cycle (menstrual cycle) in which different hormone levels rise and fall during certain times of the month. Not all of this cyclic activity is regulated in the ovaries, as many people think. Much of it is regulated in the pituitary gland, something both men and women have. But hormone levels are much more stable in males. So it would make sense that if there were pathway disturbances of a substance that directly interacted with a sex hormone, say estrogen for instance, it would not affect males and females the same. The reason? Females have very high estrogen blood concentrations at certain times of their cycle and very low concentrations at other times, whereas males have a constant and low estrogen blood concentration even during puberty when compared to females who get these great bursts of estrogen. Note: Some boys do have higher values during puberty and may start to grow breasts, which usually resolves after puberty.

    I'm not suggesting that melatonin and estrogen are the two interacting hormones. I merely used the above paragraph as an example of how the sexes could be affected differently and possibly why females are more susceptible to AIS than males. I think, don't quote me on this, that IIS and JIS are fairly evenly distributed among the sexes, so we are talking about AIS here.

    Thinking out loud here, my son had a self-resolving case of JIS. It makes me wonder if this just happens more frequently in males (self-resolving) because their hormones stabilize, whereas females with JIS start having hormone fluctuations at puberty that would make them more likely to progress. I'm just thinking out loud. If this were shown to be the case, some hormone imbalance could be the "environmental trigger". Then we would want to know what caused the hormone imbalance. This would explain how heredity could play a significant role and not produce 100% concordance in monozygotic twins. Hmmm...

    It's wee early in the morning and I haven't slept. So if this post doesn't make any sense, that's why. =)
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  10. #190
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    Rohrer, thanks for posting that. Very interesting. And complex.

    The melatonin and melatonin signaling hypotheses have been criticized and may or may not still be under active research per some papers I have read. I would have to look it up but I find scoliosis etiology research to be dense and I don't often look at it.
    Sharon, mother of identical twin girls with scoliosis

    No island of sanity.

    Question: What do you call alternative medicine that works?
    Answer: Medicine


    "We are all African."

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