Abstract WP210: Prothrombin G20210A Mutation and Ischemic Stroke Risk in European Ancestry: The Genetics of Early Onset Stroke Study and Meta-Analysis of 2304 Young-Onset Stroke Cases

Abstract

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.