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Blood, 1 July 2006, Vol. 108, No. 1, pp. 177-183. Prepublished online as a Blood First Edition Paper on March 9, 2006; DOI 10.1182/blood-2005-08-3249. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-08-3249v1 108/1/177    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Corral, J. Articles by Vicente, V. Search for Related Content PubMed PubMed Citation Articles by Corral, J. Articles by Vicente, V. Related Collections Hemostasis, Thrombosis, and Vascular Biology Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY A nonsense polymorphism in the protein Z-dependent protease inhibitor increases the risk for venous thrombosis Javier Corral, Rocio González-Conejero, Jose Manuel Soria, Jose Ramón González-Porras, Elena Pérez-Ceballos, Ramón Lecumberri, Vanessa Roldán, Juan Carlos Souto, Antonia Miñano, David Hernández-Espinosa, Ignacio Alberca, Jordi Fontcuberta, and Vicente Vicente From the Centro Regional de Hemodonación, Universidad de Murcia, Murcia, Spain; Unitat d'Hemostasia i Trombosi, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Hematology Service, Hospital Clínico Universitario, Salamanca, Spain; and Hematology Service, Clínica Universitaria de Navarra, Pamplona, Spain. 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. (Blood. 2006;108:177-183) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: U. Nowak-Gottl, B. Frohlich, S. Thedieck, A. Huge, and M. Stoll Association of the protein Z ATG haplotype with symptomatic nonvascular stroke or thromboembolism in white children: a family-based cohort study Blood, March 5, 2009; 113(10): 2336 - 2341. [Abstract] [Full Text] [PDF] J. Zhang, Y. Tu, L. Lu, N. Lasky, and G. J. Broze Jr Protein Z-dependent protease inhibitor deficiency produces a more severe murine phenotype than protein Z deficiency Blood, May 15, 2008; 111(10): 4973 - 4978. [Abstract] [Full Text] [PDF] S. Burggraf, B. Dorhofer, and B. Olgemoller Hybridization Probe Genotyping of the R67X Nonsense Polymorphism in the Protein Z-Dependent Protease Inhibitor Reveals a New R67Q Mutation Clin. Chem., July 1, 2007; 53(7): 1385 - 1387. [Full Text] [PDF] J. Corral, D. Hernandez-Espinosa, J. M. Soria, R. Gonzalez-Conejero, A. Ordonez, J. R. Gonzalez-Porras, E. Perez-Ceballos, R. Lecumberri, I. Sanchez, V. Roldan, et al. Antithrombin Cambridge II (A384S): an underestimated genetic risk factor for venous thrombosis Blood, May 15, 2007; 109(10): 4258 - 4263. [Abstract] [Full Text] [PDF]

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