Background and Purpose-It has been recently reported that a G3 A transition at nucleotide position 20210 in the 3Ј-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increased risk of deep venous thrombosis. To date, it is unknown whether this polymorphism also represents a risk factor for cerebral venous thrombosis (CVT). Methods-Venous blood samples were collected from 45 patients with CVT and from 354 healthy blood donors as controls. A second control group consisted of 131 subjects with acute ischemic stroke or transient ischemic attack (TIA). Genomic DNA was isolated from peripheral blood leukocytes. Amplification of DNA was performed by polymerase chain reaction (PCR). The G3 A transition at nucleotide position 20210 of the prothrombin gene was detected by allele-specific restriction digestion. Results-The G 20210 3 A transition in the prothrombin gene was found in a heterozygous form in 4 of 45 patients with CVT (8.9%) and in 8 of 354 healthy control subjects (2.3%). This difference was statistically significant (Pϭ0.010). The G 20210 3 A transition increased the relative risk for CVT approximately 5-fold (age-adjusted odds ratio 5.7; 95% CI 1.5 to 21.5). In contrast, in the group of patients with acute cerebral ischemia, only 3 of 131 subjects (2.3%) were heterozygous for the G 20210 3 A transition, which corresponded to the prevalence in the group of healthy blood donors. Conclusions-The recently described G 20210 3 A transition in the 3Ј-untranslated region of the prothrombin gene is an inherited risk factor for CVT but obviously not for acute ischemic stroke or TIA. (Stroke. 1998;29:1765-1769.)
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
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