title: Prothrombin G20210A mutation is associated with young-onset stroke: the genetics of early-onset stroke study and meta-analysis.
abstract: OBJECTIVE
  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 white 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 to 49 years with first-ever ischemic stroke and 426 matched controls. Logistic regression was used to calculate odds ratios (ORs) in the entire population and for subgroups stratified by sex, 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% confidence interval [CI]=0.9-6.5; P=0.07). However, among adults aged 15 to 42 years (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 aged 42 to 49 years 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.
authors.affiliation: From the Departments of Neurology (B.J., A.H., M.J.S., M.A.W., B.J.S., S.J.K., J.W.C.), Medicine (K.A.R., Y.C., P.F.M., J.R.O., B.D.M.), and Epidemiology and Public Health (O.C.S.), University of Maryland School of Medicine, Baltimore; Centers for Disease Control and Prevention, Atlanta, GA (D.K., C.J.B., M.G., W.C.H.); Department of Veterans Affairs, Veterans Affairs Medical Center Baltimore, MD (Y.C., M.A.W., B.J.S., S.J.K., J.W.C.); and Department of Veterans Affairs and Veterans Affairs Medical Center Baltimore, Geriatric Research, Education and Clinical Center, MD (B.D.M., S.J.K.).
authors.forename: Baijia
authors.initials: B
authors.lastname: Jiang
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Ryan
authors.forename: Ali
authors.initials: A
authors.lastname: Hamedani
authors.forename: Yuching
authors.initials: Y
authors.lastname: Cheng
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Sparks
authors.forename: Deborah
authors.initials: D
authors.lastname: Koontz
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Bean
authors.forename: Margaret
authors.initials: M
authors.lastname: Gallagher
authors.forename: W Craig
authors.initials: WC
authors.lastname: Hooper
authors.forename: Patrick F
authors.initials: PF
authors.lastname: McArdle
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: O'Connell
authors.forename: O Colin
authors.initials: OC
authors.lastname: Stine
authors.forename: Marcella A
authors.initials: MA
authors.lastname: Wozniak
authors.forename: Barney J
authors.initials: BJ
authors.lastname: Stern
authors.forename: Braxton D
authors.initials: BD
authors.lastname: Mitchell
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Kittner
authors.forename: John W
authors.initials: JW
authors.lastname: Cole
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002545:Brain Ischemia / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D011516:Prothrombin / Q000235:genetics*; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000235:genetics*; D044465:White People / Q000706:statistics & numerical data; D055815:Young Adult
chemical_list: D011516:Prothrombin
keywords: genetics; risk factors