Department of Clinical Laboratory, Yijishan Hospital of Wannan Medical College, Wuhu, China.
School of Laboratory Medicine, Wannan Medical College, Wuhu, China.
J Obstet Gynaecol. 2021 Oct;41(7):1053-1056. doi: 10.1080/01443615.2020.1837753. Epub 2021 Jan 11.
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, < 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 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. 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. 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.
蛋白 Z 依赖性蛋白酶抑制剂（ZPI）作为蛋白 Z 抑制 FXa 和 FXIa 的辅因子。在子痫前期（PE）患者中已经发现了蛋白 Z 的水平和多态性，但尚未报道 ZPI 的血浆水平和 ZPI 基因突变。本研究的主要目的是确定 PE 中 ZPI 的浓度和基因多态性。测定了 113 例 PE 患者（年龄：29.9±3.9 岁）和 106 例对照者（正常妊娠，年龄：27.0±2.8 岁）的 ZPI 水平。ZPI 水平通过酶联免疫吸附测定试剂盒测定，基因多态性通过聚合酶链反应和测序确定。结果表明，PE 患者的 ZPI 抗原明显低于对照组（ZPI，1.24±0.29mg/L 与 1.94±0.35mg/L，<0.05）。外显子 3 错义突变在患者和对照组中分布，这些突变与 PE 之间无明显相关性。有趣的是，观察到 ZPI 基因外显子 3 多态性 181A>G 和 481A>T 的基因型之间存在密切关系。
PE 的发生与凝血功能障碍密切相关，已知 PZ 水平降低会增加 PE 的发生概率，而 PZ 多态性与 PE 的发生无关。作为 PZ 的辅因子，与 PE 发生相关的 ZPI 的含量和多态性值得进一步研究。PE 患者的 ZPI 抗原明显低于对照组，但外显子 3 突变与 PE 之间无明显相关性。我们的结果支持 ZPI 在抗凝中起重要作用的观点，外显子 3 中的 181 基因多态性和外显子 3 中的 481 基因多态性的基因型密切相关。其他突变，如 435T>G（Phe145Leu）、972G>A（Trp324X）、1151A>G（Gln384Arg），需要进一步证实 ZPI 与包括 PE 在内的血栓前状态之间的关系。
