Prothrombin gene G20210-->A transition is a risk factor for cerebral venous thrombosis.

BACKGROUND AND PURPOSE: It has been recently reported that a G-->A transition at nucleotide position 20210 in the 3'-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 G-->A transition at nucleotide position 20210 of the prothrombin gene was detected by allele-specific restriction digestion.

RESULTS: The G20210-->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 (P=0.010). The G20210-->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 G20210-->A transition, which corresponded to the prevalence in the group of healthy blood donors.

CONCLUSIONS: The recently described G20210-->A transition in the 3'-untranslated region of the prothrombin gene is an inherited risk factor for CVT but obviously not for acute ischemic stroke or TIA.