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N Engl J Med. 2008 Apr 17;358(16):1682-91. doi: 10.1056/NEJMoa0708801. Epub 2008 Apr 9.

Effect of variation in CHI3L1 on serum YKL-40 level, risk of asthma, and lung function.

Author information

  • 1University of Chicago, Chicago, IL 60637, USA. c-ober@genetics.uchicago.edu

Abstract

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 x 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 x 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 x 10(-3) to 2.5 x 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.

Copyright 2008 Massachusetts Medical Society.

Comment in

  • Asthma and chitinases. [N Engl J Med. 2008]
PMID:
18403759
[PubMed - indexed for MEDLINE]
PMCID:
PMC2629486
Free PMC Article

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