Low protein Z levels and risk of occurrence of deep vein thrombosis

Background Protein Z (PZ) serves as a cofactor for activated FX inhibition by protein Z-dependent protease inhibitor. In vivo and in vitro studies aimed at investigating the role of PZ levels in venous thrombosis produced conflicting results. Objectives We have investigated whether reduced PZ levels and PZ gene common variants are associated with deep venous thrombosis. Patients/Methods In 197 patients with deep vein thrombosis and in 197 age- and sex-matched controls, PZ plasma levels and gene polymorphisms were evaluated by means of an enzyme-linked immunosorbant assay and direct cycle sequence analysis. Results Similar PZ levels were found in controls (1.44+0.63 μg/ml) and in patients (1.44+0.96 μg/ml). The prevalence of PZ levels below the 5.0 (0.52 μg/ml) or the 2.5 percentile of controls (0.47 μg/ml) was higher in patients (10.2 % and 8.7%, respectively) than in controls (4.1%; OR: 2.7 [95% C.I.: 1.2-7.3] and 2.0%; OR: 4.6 [95% C.I.: 1.5-13.9], respectively). This relationship was independent of the effect of age, sex, and FV Leiden and FII A20210 allele (OR: 2.8, 95% C.I.: 1.1-7.3 and 4.9, 95% C.I.: 1.4-17.3). PZ levels were associated with the intron C g–42a and the intron F g79a polymorphisms in cases (R2:0.129) and in controls (R2:0.140). However, frequencies of the PZ gene polymorphisms were similar in the two groups and were not associated with PZ very low levels . Conclusions Present data suggest an association between very low PZ plasma levels and the occurrence of deep venous thrombosis, PZ gene polymorphisms little contributing to this relationship.