Developmental and genetic regulation of human surfactant protein B in vivo.

Hamvas A, Heins HB, Guttentag SH, Wegner DJ, Trusgnich MA, Bennet KW, Yang P, Carlson CS, An P, Cole FS
Neonatology. 2009 95 (2): 117-24

PMID: 18776725 · PMCID: PMC2765709 · 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 >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.

MeSH Terms (21)

Adult Amniotic Fluid Bronchoalveolar Lavage Fluid DNA Mutational Analysis Exudates and Transudates Female Gene Expression Regulation Genetic Predisposition to Disease Gestational Age Humans Infant Infant, Newborn Infant, Premature Male Polymorphism, Single Nucleotide Protein Precursors Proteolipids Pulmonary Surfactant-Associated Protein B Respiratory Distress Syndrome, Newborn Survival Rate Trachea

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