Scientific publications

A nonsense polymorphism in the protein Z-dependent protease inhibitor increases the risk for venous thrombosis

Corral J, González-Conejero R, Soria JM, González-Porras JR, Pérez-Ceballos E, Lecumberri R, Roldán V, Souto JC, Miñano A, Hernández-Espinosa D, Alberca I, Fontcuberta J, Vicente V.
Centro Regional de Hemodonación, Universidad de Murcia, Murcia, Spain

Magazine: Blood

Date: Jul 1, 2006

Haematology and Hameotherapy

The protein Z-dependent protease inhibitor (ZPI) is a hemostatic serpin with anticoagulant activity. As for antithrombin, deficiency of ZPI could have relevant thrombotic consequences.

We have studied 6 genetic modifications affecting the ZPI gene, identifying 5 haplotypes. Haplotype H5 is featured by a stop codon at position 67. The relevance of these genetic modifications and haplotypes in venous thrombosis was evaluated in a case-control study including 1018 patients and 1018 age- and sex-matched controls. Surprisingly, the H5 haplotype was found in 0.9% of controls, supporting that the Arg67Stop change is a low frequency nonsense polymorphism. The prevalence of this haplotype increased significantly in patients (3.0%), one of whom was in a homozygous state.

Multivariate analysis confirms that carriers have a 3.3-fold risk of developing venous thrombosis (P = .002; 95% CI: 1.5-7.1). Moreover, we observed a significant association of this polymorphism with familial history of thrombosis (P < .001). Our study supports that the ZPI Arg67Stop nonsense polymorphism might be an independent genetic risk factor for venous thrombosis.

This polymorphism has slightly lower prevalence but similar thrombotic risk than the FV Leiden or prothrombin 20210A. Although further studies are required, all available data support that the ZPI is a candidate to play a significant role in thrombosis and should be evaluated in thrombophilic studies.

CITATION  Blood. 2006 Jul 1;108(1):177-83

you mayBE INTERESTED

WHAT TECHNOLOGY
DO WE USE?

The Clínica is the greater private hospital with technological equipment of Spain, all in a single center.

Imagen de un PET, tecnología de vanguardia en la Clínica Universidad de Navarra

OUR
PROFESSIONALS

The professionals of the Clínica perform continuous research and training, always to the benefit of the patient.

Imagen profesionales de la Clínica Universidad de Navarra

WHY CHOOSE
THE CLINICA?

Learn why we are different from other healthcare centers. Quality, speed, comfort and results.

Imagen del edificio de la Clínica Universidad de Navarra