title: Association of a FGFR-4 gene polymorphism with bronchopulmonary dysplasia and neonatal respiratory distress.
abstract: BACKGROUND
  Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease of premature birth, characterized by impaired alveolar development and inflammation. Pathomechanisms contributing to BPD are poorly understood. However, it is assumed that genetic factors predispose to BPD and other pulmonary diseases of preterm neonates, such as neonatal respiratory distress syndrome (RDS). For association studies, genes upregulated during alveolarization are major candidates for genetic analysis, for example, matrix metalloproteinases (MMPs) and fibroblast growth factors (FGFs) and their receptors (FGFR).
  
  
  OBJECTIVE
  Determining genetic risk variants in a Caucasian population of premature neonates with BPD and RDS. Methods. We genotyped 27 polymorphisms within 14 candidate genes via restriction fragment length polymorphism (RFLP): MMP-1, -2, -9, and -12, -16, FGF receptors 2 and 4, FGF-2, -3, -4, -7, and -18, Signal-Regulatory Protein α (SIRPA) and Thyroid Transcription Factor-1 (TTF-1).
  
  
  RESULTS
  Five single nucleotide polymorphisms (SNPs) in MMP-9, MMP-12, FGFR-4, FGF-3, and FGF-7 are associated (P < 0.05) with RDS, defined as surfactant application within the first 24 hours after birth. One of them, in FGFR-4 (rs1966265), is associated with both RDS (P = 0.003) and BPD (P = 0.023).
  
  
  CONCLUSIONS
  rs1966265 in FGF receptor 4 is a possible genetic key variant in alveolar diseases of preterm newborns.
authors.affiliation: Centre for Pediatrics and Adolescent Medicine, University of Freiburg, Mathildenstrasse 1, 79106 Freiburg, Germany.
authors.forename: Milad
authors.initials: M
authors.lastname: Rezvani
authors.forename: Juliane
authors.initials: J
authors.lastname: Wilde
authors.forename: Patricia
authors.initials: P
authors.lastname: Vitt
authors.forename: Beena
authors.initials: B
authors.lastname: Mailaparambil
authors.forename: Ruth
authors.initials: R
authors.lastname: Grychtol
authors.forename: Marcus
authors.initials: M
authors.lastname: Krueger
authors.forename: Andrea
authors.initials: A
authors.lastname: Heinzmann
mesh_terms: D001997:Bronchopulmonary Dysplasia / Q000235:genetics*; D002675:Child, Preschool; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D053505:Matrix Metalloproteinases, Secreted / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D051499:Receptor, Fibroblast Growth Factor, Type 4 / Q000235:genetics*; D012127:Respiratory Distress Syndrome, Newborn / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: C496371:FGFR4 protein, human; D051499:Receptor, Fibroblast Growth Factor, Type 4; D053505:Matrix Metalloproteinases, Secreted