title: Allele-specific N-glycosylation delays human surfactant protein B secretion in vitro and associates with decreased protein levels in vivo.
abstract: BACKGROUND
  Surfactant protein B (SP-B) is essential for normal lung function, and decreased concentrations of SP-B have a deleterious effect on pulmonary outcome. SP-B levels may correlate with variations in the encoding gene (SFTPB). SFTPB single-nucleotide polymorphism Ile131Thr affects proSP-B N-glycosylation in humans and the glycosylated Thr variant associates with pulmonary diseases.
  
  
  METHODS
  We analyzed SP-B levels in amniotic fluid samples for associations with SFTPB polymorphisms and generated cell lines expressing either proSP-B/131Ile or proSP-B/131Thr for examining the effect of glycosylation on proSP-B secretion kinetics. To determine any transcription preference between Ile131Thr allelic variants, we used heterozygous human lungs for allelic expression imbalance assays.
  
  
  RESULTS
  Protein levels correlated with Ile131Thr genotype and the lowest SP-B levels were observed in Thr/Thr homozygotes. Our results suggest that Ile131Thr variation-dependent N-glycosylation associates with decreased levels of SP-B, which is secreted from fetal lung to amniotic fluid. Glycosylated proSP-B/131Thr was secreted from transfected cells at a lower rate than nonglycosylated proSP-B/131Ile. Expression levels of the mRNA variants were equal. Secretion of the glycosylated variant was thus delayed in vitro by a posttranscriptional mechanism.
  
  
  CONCLUSIONS
  These data support the hypothesis that proSP-B glycosylation due to Ile131Thr variation may have a causal role in genetic susceptibility to acute respiratory distress.
authors.affiliation: Department of Pediatrics, Institute of Clinical Medicine, University of Oulu, Oulu, Finland.
authors.forename: Saija
authors.initials: S
authors.lastname: Taponen
authors.affiliation: Department of Pediatrics, Institute of Clinical Medicine, University of Oulu, Oulu, Finland.
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Huusko
authors.affiliation: Department of Anatomy and Cell Biology, Institute of Biomedicine, University of Oulu, Oulu, Finland.
authors.forename: Ulla E
authors.initials: UE
authors.lastname: Petäjä-Repo
authors.affiliation: 1] Department of Pediatrics, Institute of Clinical Medicine, University of Oulu, Oulu, Finland [2] Child and Adolescent Health and Welfare Unit, National Institute for Health and Welfare, Oulu, Finland.
authors.forename: Reija
authors.initials: R
authors.lastname: Paananen
authors.affiliation: Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Susan H
authors.initials: SH
authors.lastname: Guttentag
authors.affiliation: 1] Department of Pediatrics, Institute of Clinical Medicine, University of Oulu, Oulu, Finland [2] Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland.
authors.forename: Mikko
authors.initials: M
authors.lastname: Hallman
authors.affiliation: 1] Department of Pediatrics, Institute of Clinical Medicine, University of Oulu, Oulu, Finland [2] Biocenter Oulu, University of Oulu, Oulu, Finland.
authors.forename: Ritva
authors.initials: R
authors.lastname: Haataja
mesh_terms: D000483:Alleles; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006031:Glycosylation; D006801:Humans; D007532:Isoleucine / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D037701:Pulmonary Surfactant-Associated Protein B / Q000235:genetics / Q000378:metabolism*; D013912:Threonine / Q000378:metabolism
chemical_list: D037701:Pulmonary Surfactant-Associated Protein B; D007532:Isoleucine; D013912:Threonine