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Research Article | Volume 26 Issue 4 (, 2017) | Pages 460 - 466
The Role of Protein Z and Protein Z-Dependent Protease Inhibitor Polymorphisms in the Development of Prosthetic Heart Valve Thrombosis
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1
Kafkas University Medical School, Department of Cardiology, Kars, Turkey. Electronic correspondence: sleymankarakoyun@yahoo.com.tr.
2
Gaziemir State Hospital, Department of Cardiology, İzmir, Turkey.
3
Hitit University Faculty of Medicine, Department of Cardiology, Çorum, Turkey.
4
Kars Harakani State Hospital, Department of Cardiology, Kars, Turkey.
5
Kosuyolu Kartal Heart Training and Research Hospital, Department of Cardiology, İstanbul, Turkey.
6
Evliya Celebi Training and Research Hospital, Department of Cardiology, Kütahya, Turkey.
7
İstanbul Medipol University, Department of Cardiology, İstanbul, Turkey.
8
Ardahan University, Division of Health Sciences, Ardahan, Turkey.
Under a Creative Commons license
PMID : -29302946
Published
July 11, 2017
Abstract

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.

 

 

 

How to cite: Karakoyun, S., Ozan Gürsoy, M., Kalçık, M., Yesin, M., Gündüz, S., Ali Astarcıoğlu, M., Bayram, Z., Çakal, B., Bayam, E., & Özkan, M. (2017). The Role of Protein Z and Protein Z-Dependent Protease Inhibitor Polymorphisms in the Development of Prosthetic Heart Valve Thrombosis. The Journal of heart valve disease26(4), 460–466.

 
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