[HTML][HTML] Effect of Variation in CHI3L1 on Serum YKL-40 Level, Risk of Asthma, and Lung Function
C Ober, Z Tan, Y Sun, JD Possick, L Pan… - … England Journal of …, 2008 - Mass Medical Soc
C Ober, Z Tan, Y Sun, JD Possick, L Pan, R Nicolae, S Radford, RR Parry, A Heinzmann…
New England Journal of Medicine, 2008•Mass Medical SocBackground 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. Methods
We carried out a genomewide association study of serum YKL-40 levels in a founder …
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. Methods
We carried out a genomewide association study of serum YKL-40 levels in a founder …
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.
Methods
We carried out a genomewide association study of serum YKL-40 levels in a founder population of European descent, the Hutterites, and then tested for an association between an implicated SNP and asthma and lung function. One associated variant was genotyped in a birth cohort at high risk for asthma, in which YKL-40 levels were measured from birth through 5 years of age, and in two populations of unrelated case patients of European descent with asthma and controls.
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.
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