Protease activated receptor 1 (PAR1), the thrombin receptor, is implicated in hemostasis, tissue remodeling, and is critical in early placentation. PAR1 polymorphisms that influence coagulation and adhesion molecule expression may compromise formation of a normal placenta, thereby resulting in adverse outcomes. This study is a prospective, case-control comparison of Israeli mother-neonate (singletons) pairs of complicated pregnancies: 33 preterm deliveries (PTDs), 20 preeclampsia (PE), and 28 idiopathic small for gestational age neonates (SGA) versus 98 pairs of uncomplicated singleton deliveries. PCR amplification identified polymorphisms in the 5' regulatory region of the PAR1 gene at [-1426(C/T)], insertion at [-506 (I/D)], and IVS at [-14 (A/T)]. We found that 15.2% mothers with PTD were heterozygous for [-1426] versus 3% in uncomplicated deliveries; however, maternal allele frequency was not significantly different between pregnancies complicated by PE or SGA versus uncomplicated pregnancies. Maternal allele frequencies for [-506] and [-14] polymorphisms were not significantly different between any of the study groups compared to the uncomplicated group. Haplotype analysis recapitulated the genotype pattern. Maternal homozygous allele frequency for each of the polymorphic variants was low (<2%) in all pregnancies, and equally distributed. Neonatal genotypes did not differ between groups and were not associated with adverse outcomes. Maternal heterozygous allele state for PAR1 polymorphism [-1426] and the haplotype with [-506 wild-type]/[-1426T]/[IVS-14A] is associated with PTD.
Copyright 2007 Wiley-Liss, Inc.