title: CHI3L1 polymorphisms, cord blood YKL-40 levels and later asthma development.
abstract: Single nucleotide polymorphisms (SNPs) in chitinase 3-like 1 (CHI3L1), the gene encoding YKL-40, and increased serum YKL-40 levels are associated with severe forms of asthma. It has never been addressed whether SNPs in CHI3L1 and cord blood YKL-40 levels could already serve as potential biomarkers for milder forms of asthma. We assessed in an unselected population whether SNPs in CHI3L1 and cord blood YKL-40 levels at birth are associated with respiratory symptoms, lung function changes, asthma, and atopy.
  
  
  
  In a prospective birth cohort of healthy term-born neonates (n = 260), we studied CHI3L1 polymorphisms, and measured cord blood YKL-40 levels by ELISA in (n = 170) infants. Lung function was performed at 5 weeks and 6 years. Respiratory health during the first year of life was assessed weekly by telephone interviews. Diagnosis of asthma and allergic sensitisation was assessed at 6 years (n = 142).
  
  
  
  The SNP rs10399805 was significantly associated with asthma at 6 years. The odds ratio for asthma was 4.5 (95 % CI 1.59-12.94) per T-allele. This finding was unchanged when adjusting for cord blood YKL-40 levels. There was no significant association for cord blood YKL-40 levels and asthma. SNPs in CHI3L1 and cord blood YKL-40 were not associated with lung function measurements at 5 weeks and 6 years, respiratory symptoms in the first year, and allergic sensitisation at 6 years.
  
  
  
  Genetic variation in CHI3L1 might be related to the development of milder forms of asthma. Larger studies are warranted to establish the role of YKL-40 in that pathway.
authors.affiliation: University of Basel Children's Hospital, University of Basel, Basel, 4056, Switzerland.|Division of Respiratory Medicine, Department of Paediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, 3010, Switzerland.
authors.forename: Jakob
authors.initials: J
authors.lastname: Usemann
authors.affiliation: University of Basel Children's Hospital, University of Basel, Basel, 4056, Switzerland. urs.frey@ukbb.ch.
authors.forename: Urs
authors.initials: U
authors.lastname: Frey
authors.affiliation: University of Basel Children's Hospital, University of Basel, Basel, 4056, Switzerland.
authors.forename: Ines
authors.initials: I
authors.lastname: Mack
authors.affiliation: University of Basel Children's Hospital, University of Basel, Basel, 4056, Switzerland.|Division of Respiratory Medicine, Department of Paediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, 3010, Switzerland.
authors.forename: Anne
authors.initials: A
authors.lastname: Schmidt
authors.affiliation: University of Basel Children's Hospital, University of Basel, Basel, 4056, Switzerland.
authors.forename: Olga
authors.initials: O
authors.lastname: Gorlanova
authors.affiliation: Swiss Tropical and Public Health Institute Basel, Basel, 4051, Switzerland.|University of Basel, Basel, 4003, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Röösli
authors.affiliation: Children's Hospital, University of Tuebingen, Tuebingen, 72076, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Hartl
authors.affiliation: University of Basel Children's Hospital, University of Basel, Basel, 4056, Switzerland.|Division of Respiratory Medicine, Department of Paediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, 3010, Switzerland.
authors.forename: Philipp
authors.initials: P
authors.lastname: Latzin
mesh_terms: D001249:Asthma / Q000097:blood* / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D002648:Child; D000071451:Chitinase-3-Like Protein 1 / Q000097:blood* / Q000235:genetics; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D006969:Hypersensitivity, Immediate; D007231:Infant, Newborn; D016014:Linear Models; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011446:Prospective Studies; D012129:Respiratory Function Tests; D012307:Risk Factors; D013557:Switzerland
chemical_list: D015415:Biomarkers; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1
keywords: Asthma; CHI3L1 protein; Children; Cohort study; Cord blood; Genetic association study; Genetic variation; Infants; YKL-40 protein