title: 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.affiliation: University of Chicago, Chicago, IL 60637, USA. c-ober@genetics.uchicago.edu
authors.forename: Carole
authors.initials: C
authors.lastname: Ober
authors.forename: Zheng
authors.initials: Z
authors.lastname: Tan
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.forename: Jennifer D
authors.initials: JD
authors.lastname: Possick
authors.forename: Lin
authors.initials: L
authors.lastname: Pan
authors.forename: Raluca
authors.initials: R
authors.lastname: Nicolae
authors.forename: Sadie
authors.initials: S
authors.lastname: Radford
authors.forename: Rodney R
authors.initials: RR
authors.lastname: Parry
authors.forename: Andrea
authors.initials: A
authors.lastname: Heinzmann
authors.forename: Klaus A
authors.initials: KA
authors.lastname: Deichmann
authors.forename: Lucille A
authors.initials: LA
authors.lastname: Lester
authors.forename: James E
authors.initials: JE
authors.lastname: Gern
authors.forename: Robert F
authors.initials: RF
authors.lastname: Lemanske
authors.forename: Dan L
authors.initials: DL
authors.lastname: Nicolae
authors.forename: Jack A
authors.initials: JA
authors.lastname: Elias
authors.forename: Geoffrey L
authors.initials: GL
authors.lastname: Chupp
mesh_terms: D054392:Adipokines; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001249:Asthma / Q000097:blood / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D016535:Bronchial Hyperreactivity / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D000071451:Chitinase-3-Like Protein 1; D005260:Female; D018703:Founder Effect; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006023:Glycoproteins / Q000097:blood* / Q000235:genetics*; D006801:Humans; D037102:Lectins; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012123:Pulmonary Ventilation / Q000235:genetics
chemical_list: D054392:Adipokines; D015415:Biomarkers; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D037102:Lectins