Genetic association of SP-C with duration of preterm premature rupture of fetal membranes and expression in gestational tissues

Ann Med. 2009;41(8):629-42. doi: 10.1080/07853890903186176.

Abstract

Background: Surfactant protein (SP) C has been shown to be expressed also outside pulmonary alveoli. Certain SP-C gene (SFTPC) polymorphisms associate with lung diseases and very preterm birth.

Aims: We investigated the association of SFTPC single nucleotide polymorphism (SNP) rs4715 with factors affecting spontaneous preterm birth and characterized the SP-C expression in human and mouse gestational tissues.

Methods: The SFTPC SNP rs4715 polymorphism was genotyped in a homogeneous northern European population of mothers and infants in spontaneous preterm birth and term controls. The expression and protein of SP-C in gestational tissues was analyzed.

Results: SFTPC SNP rs4715 did not associate with spontaneous preterm birth. However, fetuses with short interval (<72 hours) between preterm premature rupture of fetal membranes (PPROM) and preterm birth had significant over-representation of the minor allele A, whereas in fetuses with prolonged PPROM (>or=72 hours) the frequency was decreased. Maternal SFTPC did not associate with the duration of PPROM. SP-C mRNA and proprotein were detected in fetal membranes, placenta, and pregnant uterus.

Conclusion: SFTPC SNP rs4715 associates with the duration of PPROM, and SP-C is expressed in gestational tissues. We propose that fetal SFTPC moderates the inflammatory activation within the fetal extra-embryonic compartment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Animals
  • Extraembryonic Membranes / metabolism
  • Female
  • Fetal Membranes, Premature Rupture / genetics*
  • Gene Expression*
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Middle Aged
  • Placenta / metabolism
  • Polymorphism, Single Nucleotide
  • Pregnancy
  • Premature Birth / genetics*
  • Prospective Studies
  • Pulmonary Surfactant-Associated Protein C / genetics*
  • RNA, Messenger / metabolism
  • Retrospective Studies
  • Time Factors
  • Uterus / metabolism
  • Young Adult

Substances

  • Pulmonary Surfactant-Associated Protein C
  • RNA, Messenger
  • SFTPC protein, human