title: Developmental and genetic regulation of human surfactant protein B in vivo.
abstract: BACKGROUND
  Genetic and developmental disruption of surfactant protein B (SP-B) expression causes neonatal respiratory distress syndrome (RDS).
  
  
  OBJECTIVE
  To assess developmental and genetic regulation of SP-B expression in vivo.
  
  
  METHODS
  To evaluate in vivo developmental regulation of SP-B, we used immunoblotting to compare frequency of detection of mature and pro-SP-B peptides in developmentally distinct cohorts: 24 amniotic fluid samples, unfractionated tracheal aspirates from 101 infants >or=34 weeks' gestation with (75) and without (26) neonatal RDS, and 6 nonsmoking adults. To examine genetic regulation, we used univariate and logistic regression analyses to detect associations between common SP-B (SFTPB) genotypes and SP-B peptides in the neonatal RDS cohort.
  
  
  RESULTS
  We found pro-SP-B peptides in 24/24 amniotic fluid samples and in 100/101 tracheal aspirates from newborn infants but none in bronchoalveolar lavage from normal adults (0/6) (p < 0.001). We detected an association (p = 0.0011) between pro-SP-B peptides (M(r) 40 and 42 kDa) and genotype of a nonsynonymous single nucleotide polymorphism at genomic position 1580 that regulates amino-terminus glycosylation.
  
  
  CONCLUSIONS
  Pro-SP-B peptides are more common in developmentally less mature humans. Association of genotype at genomic position 1580 with pro-SP-B peptides (M(r) 40 and 42 kDa) suggests genetic regulation of amino terminus glycosylation in vivo.
authors.affiliation: Division of Newborn Medicine, the Edward Mallinckrodt Department of Pediatrics and St. Louis Children's Hospital, St. Louis, Mo. 63110, USA. hamvas@kids.wustl.edu
authors.forename: Aaron
authors.initials: A
authors.lastname: Hamvas
authors.forename: Hillary B
authors.initials: HB
authors.lastname: Heins
authors.forename: Susan H
authors.initials: SH
authors.lastname: Guttentag
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Wegner
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Trusgnich
authors.forename: Kate W
authors.initials: KW
authors.lastname: Bennet
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Carlson
authors.forename: Ping
authors.initials: P
authors.lastname: An
authors.forename: F Sessions
authors.initials: FS
authors.lastname: Cole
mesh_terms: D000328:Adult; D000653:Amniotic Fluid / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004252:DNA Mutational Analysis; D005122:Exudates and Transudates / Q000737:chemistry / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D005865:Gestational Age; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D011510:Proteolipids / Q000235:genetics / Q000378:metabolism; D037701:Pulmonary Surfactant-Associated Protein B / Q000235:genetics* / Q000378:metabolism*; D012127:Respiratory Distress Syndrome, Newborn / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D015996:Survival Rate; D014132:Trachea / Q000378:metabolism
chemical_list: D011498:Protein Precursors; D011510:Proteolipids; D037701:Pulmonary Surfactant-Associated Protein B; C105511:surfactant protein B propeptide
references.citation: Respir Res. 2005 Jul 22;6:80
references.pmid: 16042774
references.citation: Pediatr Res. 2004 Dec;56(6):918-26
references.pmid: 15496605
references.citation: J Biol Chem. 1997 Apr 11;272(15):9640-7
references.pmid: 9092492
references.citation: J Biol Chem. 2000 Mar 24;275(12):8672-9
references.pmid: 10722708
references.citation: Hum Mutat. 2005 Nov;26(5):494-5
references.pmid: 16211553
references.citation: J Biol Chem. 2003 Dec 5;278(49):49006-14
references.pmid: 13129928
references.citation: Am J Respir Cell Mol Biol. 2003 Jan;28(1):69-79
references.pmid: 12495934
references.citation: Am J Physiol Lung Cell Mol Physiol. 2004 Feb;286(2):L382-7
references.pmid: 14578117
references.citation: Am J Respir Crit Care Med. 2003 Nov 1;168(9):1123-8
references.pmid: 12904326
references.citation: Am J Respir Crit Care Med. 2001 Oct 1;164(7):1154-60
references.pmid: 11673202
references.citation: Am J Physiol Lung Cell Mol Physiol. 2002 Aug;283(2):L452-9
references.pmid: 12114208
references.citation: N Engl J Med. 1993 Feb 11;328(6):406-10
references.pmid: 8421459
references.citation: Pediatr Int. 2002 Oct;44(5):500-4
references.pmid: 12225548
references.citation: J Clin Invest. 1994 Apr;93(4):1860-3
references.pmid: 8163685
references.citation: J Perinatol. 2005 Apr;25(4):251-7
references.pmid: 15605071
references.citation: Intern Med J. 2002 Apr;32(4):170-8
references.pmid: 11951930
references.citation: Am J Obstet Gynecol. 1994 May;170(5 Pt 1):1273-8
references.pmid: 8178852
references.citation: Biochem J. 2003 Jan 1;369(Pt 1):179-84
references.pmid: 12356334
references.citation: Pediatr Res. 2007 Aug;62(2):170-5
references.pmid: 17597650
references.citation: Annu Rev Physiol. 2001;63:555-78
references.pmid: 11181967
references.citation: Acta Paediatr. 2006 Sep;95(9):1036-48
references.pmid: 16938747
references.citation: Am J Dis Child. 1993 Jun;147(6):665-8
references.pmid: 8506837
references.citation: Am J Physiol Lung Cell Mol Physiol. 2003 Sep;285(3):L543-9
references.pmid: 12639841
references.citation: Gynecol Obstet Invest. 1994;38(1):24-7
references.pmid: 7959321
references.citation: Am J Physiol. 1998 Sep;275(3):L559-66
references.pmid: 9728051
references.citation: J Histochem Cytochem. 1992 Oct;40(10):1471-80
references.pmid: 1527371
references.citation: J Biol Chem. 2004 Apr 16;279(16):16178-84
references.pmid: 14766755
references.citation: Am J Respir Cell Mol Biol. 2004 Apr;30(4):449-58
references.pmid: 12972403
references.citation: J Biol Chem. 1996 Aug 16;271(33):19689-95
references.pmid: 8702672
references.citation: Am J Physiol Lung Cell Mol Physiol. 2001 Feb;280(2):L279-85
references.pmid: 11159007