Effect of Variation in CHI3L1 on Serum YKL-40 Level, Risk of Asthma, and Lung Function:
Background The chitinase-like protein YKL-40 is involved in inflammation and tissue remodeling. We recently showed that serum YKL-40 levels were elevated in patients with asthma and were correlated with severity, thickening of the subepithelial basement membrane, and pulmonary function. We hypothesized that single-nucleotide polymorphisms (SNPs) that affect YKL-40 levels also influence asthma status and lung function.
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Results A promoter SNP (–131C→G) in CHI3L1, the chitinase 3–like 1 gene encoding YKL-40, was associated with elevated serum YKL-40 levels (P=1.1x10–13), asthma (P=0.047), bronchial hyperresponsiveness (P=0.002), and measures of pulmonary function (P=0.046 to 0.002) in the Hutterites. The same SNP could be used to predict the presence of asthma in the two case–control populations (combined P=1.2x10–5) and serum YKL-40 levels at birth (in cord-blood specimens) through 5 years of age in the birth cohort (P=8.9x10–3 to 2.5x10–4).
Conclusions CHI3L1 is a susceptibility gene for asthma, bronchial hyperresponsiveness, and reduced lung function, and elevated circulating YKL-40 levels are a biomarker for asthma and decline in lung function.
From the discussion:
In the Hutterites, the CHI3L1 locus explains 9.4% of the variance in serum YKL-40 levels, suggesting that additional loci influence YKL-40 levels. Identifying the remaining loci that contribute to differences in serum YKL-40 levels and related proteins could identify additional genes with a significant effect on the risk of asthma and on lung function....
Remember that the Hutterites are a relatively homogenous population; and that's one reason that these researchers selected them. And of course the variance in serum levels of YKL-40 does not track perfectly the expression of the asthma disease phenotype. In other words, this is possibly a locus of some significance, but the polygenic nature of this disease susceptibility is simply confirmed. It is also important to add that it seems likely that though asthma is heritable (there are genetic predispositions), its expression seems highly contingent upon the environment. That being said, the paper does attempt to connect the dots in terms of using various techniques to converge upon a plausible answer to their question.
Finally, I was curious about the SNP which these researchers implicated in terms of increasing risk of developing asthma. It seems that Africans have more diversity around this region, so one might wonder if some between population differences exist in terms of susceptibility. Specifically, on the candidate SNP the asthma-susceptible variant is twice as common in the Yoruba sample as it is in Asians and Europeans.
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Susceptible variance is a little controversial. What little work I've done with it and in talking to colleagues who study susceptible variance in dyslexia, for instance, I'm really skeptical of these types of studies. Thanks for passing it along though.
What little work I've done with it and in talking to colleagues who study susceptible variance in dyslexia
hm. well, i give it more credence because of the molecular genetic connection they're trying to establish. a lot of the psycho-behavioral stuff doesn't seem to have that, just the correlations around QTLs....
Apart of possible genetic factors, I might have a (luckily mild) form of asthma because I was raised in a rather polluted city, because I was given antibiotics almost for any silly cough, because of overprotection against microbiological "dangers" and maybe also because of stress.
Country people very rarely have asthma. They may fall from a tree though.
I had significant asthma problems as a kid (hospitalized once after an attack) but completely outgrew it later.
I've heard that Eastern Europeans from really polluted cities have very low rates of asthma and allergies.
It's not a matter of whether it has more credence than that psycho-behavioral stuff. Of course it does. I was just saying a red flag goes up when I hear someone concludes this or that susceptible variant. I'll read the paper before going any further less I have to stick my foot in my mouth.
I was told by my doctor as a child that asthma, hay fever, and eczema were all related and genetic. In my family you can find people (at least on my mother's side) with one or the other. My mom and I had eczema, I also had hay fever (but it is has largely dissapeared after I was 16 or so, eczema decreased in severity but is still present). I had an aunt that died from having so many asthma attacks it weakened her heart and caused cardiac arrest.
To make it short, I thought this was more a issue of allergene than "lung infection", etc.
Luis,
Country people very rarely have asthma?!
I grew up in the Irish country, on a farm, and had severe asthma as a child and teenager, and have moderate chronic asthma today in middle age. I have almost died of asthma related symptoms 3 times, including being in a coma for a few days.
I had pets - dogs, cats and various other animals - was exposed to dirt - lots of it - and all other things that are supposed to reduce the risk of developing asthma. however I come from a family with lots of asthma, allergies and eczema.
Surprisingly the single biggest help to reducing asthma related symptoms was taking medication for GERD - Gastro Esophageal Reflux Disease - which seems to have stopped stomach acid getting into my lungs, which seems to have been a major irritant and trigger for attacks! So this might be a fruitful line of inquiry for some grant proposal or other?
@pconroy: Sorry if I went a bit too far. Certainly some people/families may be particularly prone to asthma and allergies because of genetic factors but, in my case, there's not a single family antecedent and yet two out of six syblings are asthmatic and allergic to "dust". Mine is milder, my brother's is quite harder.
Btw, I was just reading in the BBC that home-cleaning products may be an important factor, as irritants for sensible people. Your mention of stomach acids is quite curious too.
One thing I've noticed along time is that my own allergy/mild asthma virtually disappears in dry climates (I mean the difference between being always with a, usually wet, handkerchief at hand and not having to worry about that at all). Ambiental humidity may certainly be another factor (and this may relate to TGGP's mention of Eastern European stats). Sadly, I live in a very wet place.
I find that moist, salty air, like wind blowing off the ocean is best for me - it seems to get rid of most symptoms.
Back when they still published Wellcome Science magazine, they had a great article about asthma. They claimed that people who had suffered parasitic infections were significantly less likely to have asthma than those who hadn't. The parasites' egg sacs were coated with a substance that suppressed the immune response, as the theory went.
I find that moist, salty air, like wind blowing off the ocean is best for me - it seems to get rid of most symptoms.
There may be a difference between mere moist and salty one. I know from childhood that a salty solution (and sea water) are good for respiratory symptoms. It was even sold in pharmacies but can't recall its name right now. My mother, who was born in a family of physicians, gave it to me now and then: drops directly to the nose. And sea water works the same.
But that's not apparently contradictory to my experience that, when living in drier climates (Madrid, inner Virginia, Serbia...) the allergy symptoms disappeared in a matter of days or weeks. In contrast Bilbao is almost as wet as London or Ireland - and my nose too. :)