Hybridization Probe Genotyping of the R67X Nonsense Polymorphism in the Protein Z-Dependent Protease Inhibitor Reveals a New R67Q Mutation

Abstract

The protein Z-dependent protease inhibitor (ZPI, gene symbol SERPINA10 , serine peptidase inhibitor, clade A, member 10) inhibits the hemostatic factors Xa and XIa, and in vitro studies indicate that it is an anticoagulant (1)(2). However, the exact role of ZPI in the coagulation system is still unknown. In a recent study, 1018 patients with an episode of venous thromboembolism and 1018 controls with no history of thromboembolic disease were screened for different ZPI polymorphisms(3). A multivariant analysis, which included the Factor V Leiden mutation and the prothombin 20210 G>A sequence alteration, showed that the R67X change is an independent risk factor for venous thrombosis. The calculated odds ratios were 3.32, 5.32, and 4.24 for ZPI-R67X, Factor V Leiden, and prothombin 20210 G>A, respectively(3). We designed an assay for rapid detection of the R67X mutation that involves real-time PCR and melting point analysis on a LightCycler 1.5 Instrument. Primers (5′-CAG CTT GCC AAG GAG AC-3′ and 5′-CTC TCT TGA TCT GGG TTT CAG T-3′; NM 016186 position 686–702 and …