Background: Surfactant protein B (SP-B) is essential for normal lung function, and decreased concentrations of SP-B have a deleterious effect on pulmonary outcome. SP-B levels may correlate with variations in the encoding gene (SFTPB). SFTPB single-nucleotide polymorphism Ile131Thr affects proSP-B N-glycosylation in humans and the glycosylated Thr variant associates with pulmonary diseases.
Methods: We analyzed SP-B levels in amniotic fluid samples for associations with SFTPB polymorphisms and generated cell lines expressing either proSP-B/131Ile or proSP-B/131Thr for examining the effect of glycosylation on proSP-B secretion kinetics. To determine any transcription preference between Ile131Thr allelic variants, we used heterozygous human lungs for allelic expression imbalance assays.
Results: Protein levels correlated with Ile131Thr genotype and the lowest SP-B levels were observed in Thr/Thr homozygotes. Our results suggest that Ile131Thr variation-dependent N-glycosylation associates with decreased levels of SP-B, which is secreted from fetal lung to amniotic fluid. Glycosylated proSP-B/131Thr was secreted from transfected cells at a lower rate than nonglycosylated proSP-B/131Ile. Expression levels of the mRNA variants were equal. Secretion of the glycosylated variant was thus delayed in vitro by a posttranscriptional mechanism.
Conclusion: These data support the hypothesis that proSP-B glycosylation due to Ile131Thr variation may have a causal role in genetic susceptibility to acute respiratory distress.