A Common Polymorphism of the Protein Z Gene Is Associated With Protein Z Plasma Levels and With Risk of Cerebral Ischemia in the Young

Abstract

Background and Purpose-The vitamin K-dependent protein Z (PZ) has been shown to possess anticoagulant as well as procoagulant properties. Plasma levels of PZ show a broad interindividual variation, but it is unknown to which extent this variation is under genetic control. Recent clinical studies revealed contradictory results on the association of PZ plasma levels and the risk of ischemic stroke. Methods-We performed a case-control study including 200 patients with cerebral ischemia aged Յ50 years and 199 control subjects from the same South German region. We investigated a possible association of 2 common single nucleotide mutations in the PZ gene with the risk of cerebral ischemia. Furthermore, enzyme-linked immunosorbent assay measurements were done in control subjects without vascular disease to detect a potential association of different genotypes with PZ plasma (antigen) levels. Results-In patients, the frequency of the A allele of the intron F polymorphism G79A was significantly lower than in controls (15.7% versus 24.4%; odds ratio, 0.58; 95% CI, 0.39 to 0.86; Pϭ0.007; adjusted for age, sex, and conventional risk factors). The G allele of the promoter polymorphism A-13G tended to be less common in patients (4.2% versus 7.0%; adjusted odds ratio, 0.56; 95% CI, 0.28 to 1.13; Pϭ0.105). In 42 control subjects, the A allele of the intron F polymorphism was associated with lower PZ antigen levels (Pϭ0.0032; Spearman correlation coefficient r s ϭϪ0.48). Conclusions-The

Protein Z gene polymorphisms are associated with protein Z plasma levels

“…Interestingly, the intron A g)103a, as well as the intron F g79a polymorphism, was found to be associated with PZ plasma levels, carriers of the rare allele showing lower concentrations. These data are in agreement with recent results obtained investigating the intron F g79a polymorphism [15]. The rare intron G c24 allele Mean (SD) PZ plasma levels are expressed in lg mL )1 .…”

Tissue factor gene polymorphisms and haplotypes and the risk of ischemic vascular events: four studies and a meta‐analysis

“…Consecutive patients (n = 148) aged less than 50 years, who were admitted to the Department of Neurology, University of Heidelberg, for ischemic stroke, and control subjects (n = 191) without a history of vascular disease randomly selected from the population registries of the same region in southwest Germany were included [21]. Patients were categorized according to the Trial of Org 10172 in Acute Stroke Treatment [TOAST] criteria [22].…”

Giant arachnoid granulations

“…The G79A intron F and the A-13G polymorphisms were analyzed as previously described. 8 Factor V Leiden mutation, the MTHFR C677T, and the prothrombin G20210A polymorphisms were genotyped as previously described. [5][6][7] Statistics.…”