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

Abstract

Background: Protein Z (PZ) serves as a cofactor for activated factor X inhibition by the PZ-dependent protease inhibitor. In vivo and in vitro studies aimed at investigating the role of PZ levels in venous thombosis have produced conflicting results. Objectives: We investigated whether reduced PZ levels and PZ gene common variants are associated deep vein thrombosis (DVT). Patients and methods: In 197 patients with DVT and in 197 age-matched and sex-matched controls, PZ plasma levels and gene polymorphisms were evaluated by means of an enzyme-linked immunosorbent assay and direct cycle sequence analysis. Results: Similar PZ levels were found in controls (1.44; SD 0.63 μg mL-1) and in patients (1.44; SD 0.96 μg mL-1). The incidence of PZ levels below the 5.0 (0.52 μg mL-1) or the 2.5 percentile of controls (0.47 μg mL-1) was higher in patients (10.2% and 8.7%, respectively) than in controls {4.1% [odds ratio (OR) 2.7, 95% confidence interval (CI) 1.2-7.3], and 2.0% (OR 4.6, 95% CI 1.5-13.9), respectively}. This relationship was independent of the effect of age, sex, and factor V Leiden and FII A20210 alleles [OR 2.8 (95% CI 1.1-7.3), and OR 4.9 (95% CI 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 very low PZ levels. Conclusions: The present data suggest an association between very low PZ plasma levels and the occurrence of DVT, with PZ gene polymorphisms contributing little to this relationship. © 2006 International Society on Thrombosis and Haemostasis.