期刊
NEW ENGLAND JOURNAL OF MEDICINE
卷 358, 期 16, 页码 1682-1691出版社
MASSACHUSETTS MEDICAL SOC
DOI: 10.1056/NEJMoa0708801
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资金
- NCRR NIH HHS [M01 RR00055, M01 RR000055] Funding Source: Medline
- NHLBI NIH HHS [R01 HL072414, P50 HL056399, HL66533, HL56399, R01 HL066533, HL81638, R01 HL085197-02, HL61879, P01 HL070831, HL56389, HL72414, P01 HL056389, R01 HL085197, P50 HL056389, HL85197, U01 HL049596, HL70831] Funding Source: Medline
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.
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