Developmental and genetic regulation of human surfactant protein B in vivo.
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.
Hamvas
Aaron
A
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
Heins
Hillary B
HB
Guttentag
Susan H
SH
Wegner
Daniel J
DJ
Trusgnich
Michelle A
MA
Bennet
Kate W
KW
Yang
Ping
P
Carlson
Christopher S
CS
An
Ping
P
Cole
F Sessions
FS
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
D011498:Protein Precursors; D011510:Proteolipids; D037701:Pulmonary Surfactant-Associated Protein B; C105511:surfactant protein B propeptide
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