1 Department of Molecular Biology and Genetics - Molecular Genetics and Systems Biology, Department of Molecular Biology and Genetics, Science and Technology, Aarhus University2 Univ Southern Denmark, University of Southern Denmark, Inst Mol Med3 Odense Univ Hosp, Hans Christian Andersen Childrens Hosp4 Odense Univ Hosp, Dept Biochem5 Faculty of Science, Aarhus University, Aarhus University6 Odense Univ Hosp, Hans Christian Andersen Childrens Hosp7 Department of Molecular Biology and Genetics - Molecular Genetics and Systems Biology, Department of Molecular Biology and Genetics, Science and Technology, Aarhus University
OBJECTIVE: Associations between the genetic variation within or downstream of the surfactant protein-D-encoding gene (SFTPD), which encodes the collectin surfactant protein-D (SP-D) and may lead to respiratory distress syndrome or bronchopulmonary dysplasia, recently were reported. Our aim was to investigate whether SFTPD variations affect serum SP-D levels in infants and pulmonary outcome in premature infants. STUDY DESIGN: Serum SP-D levels were measured in 211 mature and 202 premature infants, and 7 SFTPD single-nucleotide polymorphisms (SNPs) were genotyped. SNP analysis and haplotype analysis were used to associate genetic variation to SP-D, respiratory distress (RD), oxygen requirement, and respiratory support. RESULTS: The 5'-upstream SFTPD SNP rs1923534 and the 3 structural SNPs rs721917, rs2243639, and rs3088308 were associated with the SP-D level. The same SNPs were associated with RD, a requirement for supplemental oxygen, and a requirement for respiratory support. Haplotype analyses identified 3 haplotypes that included the minor alleles of rs1923534, rs721917, and rs3088308 that exhibited highly significant associations with decreased SP-D levels and decreased ORs for RD, oxygen supplementation, and respiratory support. CONCLUSION: These findings extend and validate previous observations of SFTPD association with the risk of respiratory outcomes and suggest SFTPD as an essential factor affecting pulmonary adaptation in premature infants.
Journal of Pediatrics, 2014, Vol 165, Issue 4, p. 683-689