Prothrombin G20210A Mutant Genotype Is a Risk Factor for Cerebrovascular Ischemic Disease in Young Patients

Abstract

The factor II G20210A mutation is a recently identified congenital risk factor for venous thrombosis. Its role in artery disease is still undefined. We investigated 72 patients (35 male and 37 female) with documented ischemic stroke occurred before 50 years of age and without risk factors such as diabetes, hypertension, and hyperlipidemia; 198 thrombosis-free individuals were investigated as the control group. We found 7 heterozygotes (9.7%) and 2 homozygotes (2.7%) for the mutant factor II allele among the patients and 5 heterozygotes (2.5%) among the controls; the mutant factor II allele frequency in the patient group (7.6%, 95% confidence interval [CI], 3.3 to 11.9) was significantly higher than in the controls (1.2%; 95% CI, 0.1 to 2.3;P = .0001). The prevalence of other investigated mutant alleles (factor V G1691A, methylenetetrahydrofolate reductase C677T) did not significantly differ between the two groups. The odds ratio for ischemic stroke associated with the carriership of the mutant factor II allele (both heterozygous and homozygous genotypes) was 5.1 (95% CI, 1.6 to 16.3). Heterozygous genotype was associated with a 3.8-fold increased risk for cerebral ischemia (95% CI, 1.1 to 13.1); in particular, assuming an expected prevalence of homozygotes in the general population of 1.6 to 10,000 according to the Hardy-Weinberg equilibrium, the risk associated with the homozygous genotype was estimated exceedingly high, being increased 208-fold.

Childhood stroke in Sweden I: incidence, symptoms, risk factors and short‐term outcome

“…As opposed to many studies, we only found one case of an inherited coagulation defect, the 20210A mutation in the prothrombin gene in a girl with SVT. This mutation is associated with a two‐ to fivefold increase in the risk for, and recurrence of, venous thromboses (24,25). This girl also had anaemia and used OC, which increased her risk further.…”

Prothrombin 20210 G→A, MTHFR C677T mutations in women with venous thromboembolism associated with pregnancy

“…The increased risk of venous thromboembolism is estimated at around two‐to fourfold in heterozygotes. Interestingly, recent studies 28,29 have also demonstrated an increased risk of myocardial infarction in selected patient groups, and also an increased risk of premature stroke. To our knowledge, our data are the first to demonstrate that the prothrombin mutation is associated with maternal venous thromboembolism.…”

Does thrombophilia testing help in the clinical management of patients?

“…Findings in young stroke patients have shown inconsistent results. Patients with documented ischemic stroke before the age of 50 years and without cardiovascular risk factors were five times more likely to carry 2 G20210A than controls (De Stefano et al , 1998). A study of 468 patients with cerebrovascular disease before the age of 60 years found an elevated risk of stroke among male carriers of the F2 G20210A mutation (OR 6·1, 95% CI 1·3–28·3) but not among women (Lalouschek et al , 2005).…”