The Role of Protein Z and Protein Z-Dependent Protease Inhibitor Polymorphisms in the Development of Prosthetic Heart Valve Thrombosis

Karakoyun S., Ozan Gürsoy M., Kalçık M., Yesin M., Gündüz S., Ali Astarcıoğlu M., ...More

The Journal of heart valve disease, vol.26, no.4, pp.460-466, 2017 (Scopus) identifier identifier

  • Publication Type: Article / Article
  • Volume: 26 Issue: 4
  • Publication Date: 2017
  • Journal Name: The Journal of heart valve disease
  • Journal Indexes: Scopus
  • Page Numbers: pp.460-466
  • Istanbul Medipol University Affiliated: Yes


BACKGROUND AND AIM OF THE STUDY: Protein Z (PZ) is a vitamin K-dependent factor that is synthesized mainly by the liver. It acts as an activator of serpin, the protein Z-dependent inhibitor (ZPI), which inhibits factor Xa. The potential role of alterations in protein Z and/or ZPI levels in the pathogenesis of thrombotic and/or hemorrhagic diseases has been previously investigated, but results have been conflicting. The study aim was to evaluate the role of PZ/ZPI polymorphisms in the development of prosthetic valve thrombosis (PVT). METHODS: This prospective, observational cross-sectional study included 50 consecutive patients with PVT [non-obstructive thrombosis (NOT) in 35 patients; obstructive thrombosis (OT) in 15] and 50 consecutive healthy subjects with normally functioning prostheses. gDNA was extracted from ca. 5 × 106 leukocytes, using the QIAamp DNA Mini Kit (Qiagen), according to the manufacturer's recommendations. For mutational analysis, a minisequencing method was employed. Results of the analyses were compared between the PVT and control groups, and also between the OT and NOT subgroups. RESULTS: The frequency of A allele (mutant type) of PZG79A was equal in all PVT patients and in controls. With regards to PZ-A13G polymorphisms, frequency of the mutant G allele was 22% in PVT patients and 19% in controls. Serpina-R67X polymorphism was observed in 8% of PVT patients and 6% of controls. Normal variant CC was present in 47 controls (94%), whereas a heterozygotic mutation (CT) was detected in four PVT patients (8%). Frequency of the ZPI-R67X mutation was significantly higher in patients with OT than in those with NOT (p = 0.041). CONCLUSIONS: The present study was the first to evaluate the potential impact of PZ (PZ-A13G, PZG79A) and ZPI (R-67X, W303X) polymorphisms in the development of PVT. Based on the results of this small observational case-control study, PZ/ZPI polymorphisms do not appear to play an active role in the development of PVT. Hence, further extensive studies are necessary.