Developmental and Genetic Regulation of Human Surfactant Protein B in vivo

• Published in: Neonatology (Basel, Switzerland) Vol. 95; no. 2; pp. 117 - 124
• Main Authors: Hamvas, Aaron, Heins, Hillary B., Guttentag, Susan H., Wegner, Daniel J., Trusgnich, Michelle A., Bennet, Kate W., Yang, Ping, Carlson, Christopher S., An, Ping, Cole, F. Sessions
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.02.2009
• Subjects: Adult; Amniotic Fluid - metabolism; Bronchoalveolar Lavage Fluid - chemistry; DNA Mutational Analysis; Exudates and Transudates - chemistry; Exudates and Transudates - metabolism; Female; Gene Expression Regulation; Genetic Predisposition to Disease; Gestational Age; Humans; Infant; Infant, Newborn; Infant, Premature; Male; Original Paper; Polymorphism, Single Nucleotide; Protein Precursors - genetics; Protein Precursors - metabolism; Proteolipids - genetics; Proteolipids - metabolism; Pulmonary Surfactant-Associated Protein B - genetics; Pulmonary Surfactant-Associated Protein B - metabolism; Respiratory Distress Syndrome, Newborn - genetics; Respiratory Distress Syndrome, Newborn - metabolism; Respiratory Distress Syndrome, Newborn - mortality; Survival Rate; Trachea - metabolism; Respiratory distress syndrome; Surfactant proteins; Neonatal respiratory diseases
• ISSN: 1661-7800; 1661-7819
• DOI: 10.1159/000153095

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 (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.