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Updated: Apr 19, 2026

Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
Published on: June 21, 2018
Protease-activated-receptor 1 polymorphisms correlate with risk for unexplained recurrent pregnancy loss: a pilot
Sorina Grisaru-Granovsky1, Zaidoun Salah2, Miriam Maoz2
1Division of Maternal Fetal Medicine, Shaare Zedek Medical Center; Jerusalem, Israel.
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.
Objectives:
To analyze whether polymorphisms of PAR1 [-1426C/T], [-506I/D], and/or IVS[-14A/T] are associated with unexplained RPL.
Patients/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.
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