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


OBJECTIVE
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.


CONCLUSIONS
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.
Salminen
Annamari
A
Institute of Clinical Medicine, Department of Pediatrics, Biocenter Oulu, University of Oulu, FIN-90014, Oulu, Finland.
Paananen
Reija
R
Karjalainen
Minna K
MK
Tuohimaa
Anu
A
Luukkonen
Aino
A
Ojaniemi
Marja
M
Jouppila
Pentti
P
Glasser
Stephan
S
Haataja
Ritva
R
Vuolteenaho
Reetta
R
Hallman
Mikko
M
D000293:Adolescent; D000328:Adult; D000483:Alleles; D000818:Animals; D005321:Extraembryonic Membranes / Q000378:metabolism; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D010920:Placenta / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D047928:Premature Birth / Q000235:genetics*; D011446:Prospective Studies; D037721:Pulmonary Surfactant-Associated Protein C / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D012189:Retrospective Studies; D013997:Time Factors; D014599:Uterus / Q000378:metabolism; D055815:Young Adult
D037721:Pulmonary Surfactant-Associated Protein C; D012333:RNA, Messenger; C489679:SFTPC protein, human