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Developmental and Genetic Regulation of Human Surfactant Protein B in vivoHamvas A.a · Heins H.B.a · Guttentag S.H.d · Wegner D.J.a · Trusgnich M.A.a · Bennet K.W.a · Yang P.a · Carlson C.S.c · An P.b · Cole F.S.a
aDivision of Newborn Medicine, the Edward Mallinckrodt Department of Pediatrics and St. Louis Children’s Hospital, bDivision of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, Mo., cDivision of Public Health Sciences, the Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Wash., and dDivision of Neonatology, Department of Pediatrics, The Children’s Hospital of Philadelphia and the University of Pennsylvania School of Medicine, Philadelphia, Pa., USA Corresponding Author
Aaron Hamvas, MD
Division of Newborn Medicine, St. Louis Children’s Hospital
One Children’s Place
St. Louis, MO 63110 (USA)
Tel. +1 314 454 6148, Fax +1 314 454 4633, E-Mail email@example.com
Background: Genetic and developmental disruption of surfactant protein B (SP-B) expression causes neonatal respiratory distress syndrome (RDS). Objectives: 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 ≥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 (Mr 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 (Mr 40 and 42 kDa) suggests genetic regulation of amino terminus glycosylation in vivo.
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