title: Polymorphisms of the gene encoding Kit ligand are associated with bronchopulmonary dysplasia.
abstract: Bronchopulmonary dysplasia (BPD) is a chronic inflammatory lung disease that affects infants born preterm. Family studies indicate that BPD has a significant genetic component.
  
  
  BACKGROUND
  We assessed the gene encoding Kit ligand (KITLG) as a candidate for genetic predisposition to moderate-to-severe BPD (controls were infants with no or mild BPD).
  
  
  METHODS
  Eight KITLG-tagging single nucleotide polymorphisms (SNPs) were analyzed in cohorts of very preterm infants originating from northern Finland (56 cases and 197 controls), southern Finland (n = 59 + 52), and Canada (n = 58 + 68). Additional replication populations included infants born in Finland (n = 41 + 241) and Hungary (n = 29 + 40). All infants were of European origin. Results were controlled for risk factors of BPD. Kit ligand concentration in umbilical cord blood, collected from very preterm infants (n = 120), was studied.
  
  
  RESULTS
  Six SNPs of KITLG and a haplotype including all eight genotyped SNPs were associated with moderate-to-severe BPD in the northern Finnish population. When all the populations were combined, SNP rs11104948 was significantly associated with BPD. Kit ligand concentration in umbilical cord blood of infants born very preterm was an independent risk factor of BPD.
  
  
  CONCLUSIONS
  We show that KITLG polymorphisms are associated with susceptibility to moderate-to-severe BPD. In addition, higher Kit ligand concentrations were observed in infants that subsequently developed BPD. These results support the possibility that KITLG gene is involved in predisposition to BPD. Pediatr Pulmonol. 2015; 50:260-270. © 2014 Wiley Periodicals, Inc.
authors.affiliation: Department of Pediatrics, Institute of Clinical Medicine, and Medical Research Center Oulu, University of Oulu, Oulu, Finland.|Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland.
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Huusko
authors.affiliation: Department of Pediatrics, Institute of Clinical Medicine, and Medical Research Center Oulu, University of Oulu, Oulu, Finland.|Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland.
authors.forename: Mari
authors.initials: M
authors.lastname: Mahlman
authors.affiliation: Department of Pediatrics, Institute of Clinical Medicine, and Medical Research Center Oulu, University of Oulu, Oulu, Finland.|Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland.
authors.forename: Minna K
authors.initials: MK
authors.lastname: Karjalainen
authors.affiliation: Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland.
authors.forename: Tuula
authors.initials: T
authors.lastname: Kaukola
authors.affiliation: Department of Pediatrics, Institute of Clinical Medicine, and Medical Research Center Oulu, University of Oulu, Oulu, Finland.
authors.forename: Ritva
authors.initials: R
authors.lastname: Haataja
authors.affiliation: Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland.
authors.forename: Riitta
authors.initials: R
authors.lastname: Marttila
authors.affiliation: First Department of Pediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: Gergely
authors.initials: G
authors.lastname: Toldi
authors.affiliation: First Department of Pediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Szabó
authors.affiliation: Center for Pediatric Genomic Medicine, Kansas City, Missouri.
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Kingsmore
authors.affiliation: Department of Pediatrics, Institute of Clinical Medicine, and Medical Research Center Oulu, University of Oulu, Oulu, Finland.|Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland.|Institute of Biomedical Technology, and BioMediTech, University of Tampere, Finland.|Department of Pediatrics, Tampere University Hospital, Tampere, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Rämet
authors.affiliation: Child & Family Research Institute of British Columbia, Vancouver, Canada.
authors.forename: Pascal M
authors.initials: PM
authors.lastname: Lavoie
authors.affiliation: Department of Pediatrics, Institute of Clinical Medicine, and Medical Research Center Oulu, University of Oulu, Oulu, Finland.|Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland.
authors.forename: Mikko
authors.initials: M
authors.lastname: Hallman
keywords: preterm infant; single nucleotide polymorphisms; stem cell factor