Effect of variation in CHI3L1 on serum YKL-40 level, risk of asthma, and 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, Dan L Nicolae, Jack A Elias, Geoffrey L Chupp | | Language: | Eng. | | Date: | 18-04-2008 | | Journal: | The New England journal of medicine
(1533-4406)
| | Release: | N Engl J Med. 2008 Apr;358(16):1682-91 | |
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Abstract:
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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: | The New England journal of medicine
University of Chicago, Chicago, IL 60637, USA. c-ober@genetics.uchicago.edu | | Full text: |  EBSCO - HTML (needs subscription) | | Terms: | Adolescent, Adult, Aged, Aged, 80 and over, Asthma, Biological Markers, Bronchial Hyperreactivity, Case-Control Studies, Child, Female, Founder Effect, Genetic Predisposition to Disease, Genotype, Glycoproteins, Humans, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Pulmonary Ventilation | | |
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