Background and Purpose Although the prothrombin G20210A mutation has been implicated as a risk factor for venous thrombosis, its role in arterial ischemic stroke is unclear, particularly among young-adults. To address this issue, we examined the association between prothrombin G20210A and ischemic stroke in a Caucasian case-control population and additionally performed a meta-analysis Methods From the population-based Genetics of Early Onset Stroke (GEOS) study we identified 397 individuals of European ancestry aged 15-49 years with first-ever ischemic stroke and 426 matched-controls. Logistic regression was used to calculate odds ratios in the entire population and for subgroups stratified by gender, age, oral contraceptive use, migraine and smoking status. A meta-analysis of 17 case-control studies (n=2305 cases <55 years) was also performed with and without GEOS data. Results Within GEOS, the association of the prothrombin G20210A mutation with ischemic stroke did not achieve statistical significance (OR=2.5,95%CI=0.9-6.5,p=0.07). However, among adults aged 15-42 (younger than median age), cases were significantly more likely than controls to have the mutation (OR=5.9,95%CI=1.2-28.1,p=0.03), whereas adults ages 42-49 were not (OR=1.4,95%CI=0.4-5.1,p=0.94). In our meta-analysis, the mutation was associated with significantly increased stroke risk in adults <=55 years (OR=1.4;95%CI=1.1-1.9;p=0.02) with significance increasing with addition of the GEOS results (OR=1.5;95%CI=1.1-2.0;p=0.005). Conclusions The prothrombin G20210A mutation is associated with ischemic stroke in young-adults and may have an even stronger association among those with earlier onset strokes. Our finding of a stronger association in the younger-young adult population requires replication.

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Background: Although the prothrombin G20210A mutation has been implicated in increased risk for venous thrombosis, its role in arterial ischemic stroke is unclear, particularly among young adults. To address this issue, we examined the association between prothrombin G20210A and ischemic stroke in Caucasian participants of the Genetics of Early Onset Stroke (GEOS) Study (n=396 cases) and also performed a meta-analysis of 17 case-control studies (n=2304 cases) examining the effect of prothrombin G20210A on ischemic stroke risk in young adults (<55 years). Methods: A population-based case-control study identified 396 cases of women and men 15 to 49 years of age of European ancestry with first-ever ischemic stroke and 426 matched controls. Logistic regression was used to calculate odds ratios for the entire population and for subgroups stratified by gender, oral contraceptive use, smoking status, and age category. Results: In the GEOS study, the prothrombin G20210A mutation was associated with a large but non-significant increase in ischemic stroke risk (OR=2.4, 95% CI: 0.9-6.5, p=0.08). However, among adults aged 15-42 (younger than the median age), cases were significantly more likely to have the prothrombin mutation than controls (OR=5.9, 95% CI: 1.1-28.5, p=0.03), whereas adults ages 42-49 were not (OR 1.1, 95% CI 0.3-4.4, p=0.94). In the meta-analysis of prior studies, the prothrombin G20210A mutation was significantly associated with stroke risk (OR 1.4, 95% CI: 1.1-1.9, p=0.02) with these results increasing in precision with addition of the GEOS results (OR=1.5, 95% CI: 1.1-2.0, p=0.005). Conclusion: The prothrombin mutation is associated with ischemic stroke in young adults. The GEOS data suggests that, within the young adult age range, the prothrombin G20210A mutation may have an even stronger association among those with the earliest onset strokes. The finding of a stronger association in the ‘younger’ young adult population requires replication in other studies.