Plasma concentration of protein Z-dependent protease inhibitor and ZPI exon 3 mutations in preeclampsia

Abstract

Protein Z-dependent protease inhibitor (ZPI) serves as a cofactor of inhibition of FXa and FXIa by protein Z. The levels of protein Z and polymorphisms have been shown in preeclampsia (PE) patients, but the plasma levels of ZPI and ZPI gene mutations were not reported yet. The principal aim of this study was to identify the concentration of ZPI and gene polymorphism in PE. ZPI levels were determined in 113 PE patients (age: 29.9 ± 3.9 years) and in 106 controls (normal pregnancy, age: 27.0 ± 2.8 years). ZPI was measured by enzyme-linked immunosorbent assay kit, and the gene polymorphism was determined by polymerase chain reaction and sequencing. The results showed ZPI antigen was found to be significantly lower in PE patients than in controls (ZPI, 1.24 ± 0.29 mg/L vs. 1.94 ± 0.35 mg/L, p < 0.05). The exon-3 missense mutations were distributed in patients and controls and there was no convincing correlation between these mutations and PE. It was of interest to observe a close relationship between the genotypes of the exon 3 polymorphisms 181 A > G and 481 A > T in the ZPI gene. Impact statement What is already known on this subject? The occurrence of PE is closely related to dysfunction of coagulation, and it is known that the decrease of PZ level can increase the occurrence probability of PE, while the polymorphism of PZ is not related to the occurrence of PE. As a cofactor of PZ, the content and polymorphism of ZPI which related to the occurrence of PE is worth further study. What the results of this study add? ZPI antigen was found to be significantly lower in PE patients than in controls, but there was no convincing correlation between exon-3 mutations and PE. What the implications are of these findings for clinical practice and/or further research? Our results support the view that ZPI plays a significant role in anticoagulant, and the genotype of the 181 gene polymorphism in exon-3 and 481 gene polymorphism in exon-3 are closely related. Other mutations like 435T > G(Phe145Leu), 972G > A(Trp324X), 1151A > G(Gln384Arg) are necessary to confirm the association between ZPI and prothrombotic state including PE.