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

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

Neonatology (2008-09-09)
Aaron Hamvas, Hillary B Heins, Susan H Guttentag, Daniel J Wegner, Michelle A Trusgnich, Kate W Bennet, Ping Yang, Christopher S Carlson, Ping An, F Sessions Cole

Genetic and developmental disruption of surfactant protein B (SP-B) expression causes neonatal respiratory distress syndrome (RDS). To assess developmental and genetic regulation of SP-B expression in vivo. 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. 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. 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.

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