Surfactant Protein-D–Encoding Gene Variant Polymorphisms Are Linked to Respiratory Outcome in Premature Infants

• Published in: The Journal of pediatrics 2014-10, Vol.165 (4), p.683-689
• Main Authors: Sorensen, Grith Lykke, PhD, Dahl, Marianne, MD, Tan, Qihua, PhD, Bendixen, Christian, PhD, Holmskov, Uffe, DMSc, Husby, Steffen, DMSc
• Format: Article
• Language: English
• Subjects: Alleles; Birth Weight; Bronchopulmonary Dysplasia - genetics; Cohort Studies; Enzyme-Linked Immunosorbent Assay; Female; Genetic Variation; Genotype; Gestational Age; Haplotypes; Humans; Infant, Newborn; Infant, Premature; Male; Oxygen - therapeutic use; Pediatrics; Polymorphism, Genetic; Pulmonary Surfactant-Associated Protein D - genetics; Respiration; Respiratory Distress Syndrome, Newborn - genetics; Treatment Outcome
• ISSN: 0022-3476; 1097-6833
• DOI: 10.1016/j.jpeds.2014.05.042

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.