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 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.
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 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: Ali G Hamedani; John W Cole; Yuching Cheng; Mary J Sparks; Jeffrey R O'Connell; Oscar C Stine; Marcella A Wozniak; Barney J Stern; Braxton D Mitchell; Steven J Kittner Journal: J Stroke Cerebrovasc Dis Date: 2011-11-18 Impact factor: 2.136
Authors: R Grossmann; U Geisen; G Merati; W Müllges; C M Schambeck; U Walter; S Schwender Journal: Blood Coagul Fibrinolysis Date: 2002-10 Impact factor: 1.276
Authors: S J Kittner; B J Stern; B R Feeser; R Hebel; D A Nagey; D W Buchholz; C J Earley; C J Johnson; R F Macko; M A Sloan; R J Wityk; M A Wozniak Journal: N Engl J Med Date: 1996-09-12 Impact factor: 91.245
Authors: Pasquale Madonna; Valentino de Stefano; Antonio Coppola; Ferdinando Cirillo; Anna Maria Cerbone; Giuseppe Orefice; Giovanni Di Minno Journal: Stroke Date: 2002-01 Impact factor: 7.914
Authors: Ivan Bank; Eduard J Libourel; Saskia Middeldorp; Elisabeth C M Van Pampus; Maria M W Koopman; Karly Hamulyák; Martin H Prins; Jan Van Der Meer; Harry R Büller Journal: Arch Intern Med Date: 2004-09-27
Authors: Jukka Putaala; Nicolas Martinez-Majander; Sahrai Saeed; Nilufer Yesilot; Pekka Jäkälä; Ossi Nerg; Georgios Tsivgoulis; Heikki Numminen; Daniel Gordin; Bettina von Sarnowski; Ulrike Waje-Andreassen; Pauli Ylikotila; Risto O Roine; Marialuisa Zedde; Juha Huhtakangas; Catarina Fonseca; Petra Redfors; Frank-Erik de Leeuw; Alessandro Pezzini; Janika Kõrv; Siim Schneider; Christian Tanislav; Christian Enzinger; Dalius Jatuzis; Bob Siegerink; Patricia Martínez-Sánchez; Armin J Grau; Frederick Palm; Per-Henrik Groop; Sylvain Lanthier; Hugo Ten Cate; Pirkko Pussinen; Susanna Paju; Juha Sinisalo; Mika Lehto; Arne Lindgren; José Ferro; Steven Kittner; Franz Fazekas; Eva Gerdts; Turgut Tatlisumak Journal: Eur Stroke J Date: 2017-04-04
Authors: John W Cole; Huichun Xu; Kathleen Ryan; Thomas Jaworek; Nicole Dueker; Patrick McArdle; Brady Gaynor; Yu-Ching Cheng; Jeffrey O'Connell; Steve Bevan; Rainer Malik; Naveed Uddin Ahmed; Philippe Amouyel; Sheraz Anjum; Joshua C Bis; David Crosslin; John Danesh; Stefan T Engelter; Myriam Fornage; Philippe Frossard; Christian Gieger; Anne-Katrin Giese; Caspar Grond-Ginsbach; Weang Kee Ho; Elizabeth Holliday; Jemma Hopewell; M Hussain; W Iqbal; S Jabeen; Jim Jannes; Ayeesha Kamal; Yoichiro Kamatani; Sandip Kanse; Manja Kloss; Mark Lathrop; Didier Leys; Arne Lindgren; W T Longstreth; Khalid Mahmood; Christa Meisinger; Tiina M Metso; Thomas Mosley; Martina Müller-Nurasyid; Bo Norrving; Eugenio Parati; Annette Peters; Alessandro Pezzini; I Quereshi; Asif Rasheed; A Rauf; T Salam; Jess Shen; Agnieszka Słowik; Tara Stanne; Konstantin Strauch; Turgut Tatlisumak; Vincent N Thijs; Steffen Tiedt; Matthew Traylor; Melanie Waldenberger; Matthew Walters; Wei Zhao; Giorgio Boncoraglio; Stéphanie Debette; Christina Jern; Christopher Levi; Hugh Markus; James Meschia; Arndt Rolfs; Peter Rothwell; Danish Saleheen; Sudha Seshadri; Pankaj Sharma; Cathie Sudlow; Bradford Worrall; O Colin Stine; Steven J Kittner; Braxton D Mitchell Journal: PLoS One Date: 2018-11-01 Impact factor: 3.240