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=1.1×10–13), 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=1.2×10–5) and serum YKL-40 levels at birth (in cord-blood specimens) through 5 years of age in the birth cohort (P=8.9×10–3 to 2.5×10–4).
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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