title: Protease-activated-receptor 1 polymorphisms correlate with risk for unexplained recurrent pregnancy loss: a pilot study querying an association beyond coagulation.
abstract: BACKGROUND
  Recurrent pregnancy loss (RPL) has been associated with impaired maternal-fetal communication. Protease-activated-receptor 1 (PAR1) is critical for trophoblast invasion and establishment unrelated to its role in vascular biology.
  
  
  OBJECTIVE
  To analyze whether polymorphisms of PAR1 [-1426C/T], [-506I/D], and/or IVS[-14A/T] are associated with unexplained RPL.
  
  
  METHODS
  A case-control pilot study conducted in 39 healthy women with history of unexplained RPL and 98 women with a full-term, uncomplicated deliveries and no history of RPL.
  
  
  RESULTS
  Women with RPL were significantly more likely to be heterozygous for [-1426C/T] (12.8% versus 3.2%; p=0.049); the heterozygous state for IVS[-14A/T] was also more common (15.4% versus 4.4%; p=0.064). There was no difference between groups for [-506I/D] genotypes. The functional consequence for [-1426C/T] and IVS[-14A/T] polymorphisms is underscored by the markedly low PAR1 mRNA levels in those women. Bioinformatics indicate generation of a new consensus motif for repressor Kruppel-like factor 3 (KLF3) in [-1426T]. Moreover, chromatin immunoprecipitation (ChIP) analysis confirmed a physical association between KLF3 protein and the hPar1 DNA obtained from women with the [-1426C/T] polymorphism.
  
  
  CONCLUSIONS
  We hypothesize that the significantly low PAR1 levels impact placenta establishment and consequently pregnancy outcome, thereby profiling a novel risk factor for unexplained RPL.
authors.affiliation: Division of Maternal Fetal Medicine, Shaare Zedek Medical Center; Jerusalem, Israel. Electronic address: granovs@012.net.il.
authors.forename: Sorina
authors.initials: S
authors.lastname: Grisaru-Granovsky
authors.affiliation: Department of Oncology and Tumor Biology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Zaidoun
authors.initials: Z
authors.lastname: Salah
authors.affiliation: Department of Oncology and Tumor Biology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Miriam
authors.initials: M
authors.lastname: Maoz
authors.affiliation: Division of Maternal Fetal Medicine, Shaare Zedek Medical Center; Jerusalem, Israel.
authors.forename: Aharon
authors.initials: A
authors.lastname: Tevet
authors.affiliation: Reproductive Endocrinology and Clinic for Repeated Pregnancy Loss, Shaare Zedek Medical Center; Jerusalem, Israel.
authors.forename: Ehud
authors.initials: E
authors.lastname: Margalioth
authors.affiliation: Division of Maternal Fetal Medicine, Shaare Zedek Medical Center; Jerusalem, Israel.
authors.forename: Arnon
authors.initials: A
authors.lastname: Samueloff
authors.affiliation: Human Genetics Unit, Shaare Zedek Medical Center; Jerusalem, Israel.
authors.forename: Gheona
authors.initials: G
authors.lastname: Altarescu
authors.affiliation: Department of Oncology and Tumor Biology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Rachel
authors.initials: R
authors.lastname: Bar-Shavit
mesh_terms: D000026:Abortion, Habitual / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D001483:Base Sequence; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D008969:Molecular Sequence Data; D010865:Pilot Projects; D011110:Polymorphism, Genetic; D011247:Pregnancy; D044463:Receptor, PAR-1 / Q000235:genetics*
chemical_list: C501168:KLF3 protein, human; D051741:Kruppel-Like Transcription Factors; D044463:Receptor, PAR-1
keywords: Kruppel-like factor 3; Polymorphic variants; Protease-activated-receptor 1; Recurrent pregnancy loss; Trophoblast