Prothrombin G20210A Mutation Is Associated With Young-Onset Stroke

Abstract

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.

Ischemic Stroke in Young Adults of Northern China: Characteristics and Risk Factors for Recurrence

“…Burden of vascular risk factors, family history of cardiovascular disease, and increased intima-media thickness of the internal carotid artery have been reported to be risk factors for ischemic stroke in young and middle aged adults (15-60 years) [6]. It has also been reported that certain genetic mutation (prothrombin G20210A) was associated with ischemic stroke in young adults [7]. A review of data from population-based studies in the United States identified increasing prevalence of stroke risk factors among persons aged 15-44 years of age, including hypertension, diabetes mellitus, obesity, lipid disorders, congenital heart disease, and smoking [8].…”

Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Triggers, Causes, and Outcome (SECRETO): Rationale and design

“…One of the most examined aggregate of risk factors is the combination of PFO and prothrombotic mutations. 9 However, with or without PFO, the role of known prothrombotic mutations and other investigated candidate genes remains inconclusive, [10][11][12] whereas data suggest that genetic factors have a much stronger influence in early-onset rather than late-onset IS. 13 Due to the large proportion of cryptogenic events, the evidence base to guide prevention and treatment of early-onset IS remains poor.…”

The association of hemostasis system genes with the development of ischemic stroke in patients under the age of 50 years

“…Большинство исследований в отношении полиморфизма G20210A гена F2 не выявило ассоциации с риском развития ИИ [16,18,30]. Однако результаты исследовании GEOS [15] показали ассоциацию данного полиморфного локуса с ИИ у пациентов молодого возраста. В настоящем исследовании также были получены данные, что полиморфизм G20210A гена F2 не ассоциирован с риском развития ИИ у пациентов в возрасте до 50 лет.…”

“…В ряде исследований [12,14] была выявлена ассоциация G20210A полиморфизма гена F2 с риском развития тромбоза вен нижних конечностей. В отношении данного полиморфного локуса и риска развития ИИ имеются достаточно противоречивые данные [15][16][17][18].…”

“…Результаты исследований по изучению влияния полиморфных вариантов генов GP1BA, F2, F5 на риск развития ИИ не являются однозначными [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]. Возможно, это связано со значительными межэтническими различиями в распределении генотипов и аллелей однонуклеотидных полиморфизмов генов в разных популяциях.…”