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Am J Physiol Lung Cell Mol Physiol 292: L448-L453, 2007. First published October 27, 2006; doi:10.1152/ajplung.00307.2006 Free Article
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The C/A(–18) polymorphism in the surfactant protein B gene influences transcription and protein levels of surfactant protein B

Wendy K. Steagall,1 Jing-Ping Lin,2 and Joel Moss1

1Pulmonary-Critical Care Medicine Branch and 2Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland

Submitted 10 August 2006 ; accepted in final form 26 October 2006

Surfactant protein B (SP-B) is an essential component of surfactant that promotes adsorption and spreading of surfactant phospholipids and stabilizes the phospholipid monolayer. SP-B is essential for respiratory function in newborn humans and mice; adult mice with levels of SP-B below 25% of wild-type develop fatal respiratory distress syndrome. A potential regulatory function of the C/A(–18) single nucleotide polymorphism (SNP) in the promoter of the SP-B gene was examined. Transcriptional analysis and ELISA on bronchoalveolar lavage fluid revealed that the presence of the C allele correlated with more SP-B promoter activity and protein. There was approximately threefold difference in amounts of SP-B in bronchoalveolar lavage fluid from CA(–18) and AA(–18) individuals. By EMSA, Sp1 bound more tightly to the C allele sequence than to the A allele sequence, perhaps accounting for the differences in transcription. Genotyping of a normal volunteer population showed ~31% of the population were AA homozygotes, suggesting that these individuals produce less SP-B. Differences in amounts of SP-B resulting from the promoter SNP could affect the clinical presentation of pulmonary disease.

electrophoretic mobility shift assay; enzyme-linked immunosorbent assay; respiratory function; SFTPB



Address for reprint requests and other correspondence: J. Moss, Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bldg. 10, Rm. 6D03, MSC 1590, Bethesda, MD 20892-1590 (e-mail: mossj{at}nhlbi.nih.gov)




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