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

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.

• Authors: Carole Ober, Zheng Tan, Ying Sun, Jennifer D Possick, Lin Pan, Raluca Nicolae, Sadie Radford, Rodney R Parry, Andrea Heinzmann, Klaus A Deichmann, Lucille A Lester, James E Gern, Robert F Lemanske Jr, Dan L Nicolae, Jack A Elias, Geoffrey L Chupp
• Journal: The New England journal of medicine (N Engl J Med) Vol. 358 Issue 16 Pg. 1682-91 (Apr 17 2008) ISSN: 1533-4406 [Electronic] United States
• PMID: 18403759 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright 2008 Massachusetts Medical Society.

Chemical References

• Adipokines
• Biomarkers
• CHI3L1 protein, human
• Chitinase-3-Like Protein 1
• Glycoproteins
• Lectins

Topics

• Adipokines
• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Asthma (blood, genetics)
• Biomarkers (blood)
• Bronchial Hyperreactivity (blood, genetics)
• Case-Control Studies
• Child
• Chitinase-3-Like Protein 1
• Female
• Founder Effect
• Genetic Predisposition to Disease
• Genotype
• Glycoproteins (blood, genetics)
• Humans
• Lectins
• Male
• Middle Aged
• Phenotype
• Polymorphism, Single Nucleotide
• Pulmonary Ventilation (genetics)