Jamary Oliveira-Filho1, Ana C P Ornellas2, Cathy R Zhang3, Luciana M B Oliveira2, Théo Araújo-Santos4, Valeria M Borges5, Laís M G B Ventura2, Francisco J F B Reis6, Roque Aras6, André M Fernandes6, Jonathan Rosand3, Steven M Greenberg3, Karen L Furie7, Natalia S Rost3. 1. Stroke and Cardiomyopathy Clinics, Federal University of Bahia, Salvador, Brazil; Instituto Nacional de Ciencia e Tecnologia em Doencas Tropicais (INCT-DT), Brazilian National Research Committee (CNPq), Salvador, Brazil. Electronic address: jamary@mail.harvard.edu. 2. Stroke and Cardiomyopathy Clinics, Federal University of Bahia, Salvador, Brazil; Instituto Nacional de Ciencia e Tecnologia em Doencas Tropicais (INCT-DT), Brazilian National Research Committee (CNPq), Salvador, Brazil. 3. Stroke Division, Massachusetts General Hospital, Boston, USA. 4. Universidade Federal do Oeste da Bahia (UFOB), Barreiras, Brazil. 5. Centro de Pesquisas Goncalo Moniz, Oswaldo Cruz Foundation-Bahia (CPqGM, FIOCRUZ-BA), Salvador, Brazil. 6. Stroke and Cardiomyopathy Clinics, Federal University of Bahia, Salvador, Brazil. 7. Department of Neurology, Brown University, Providence, USA.
Abstract
BACKGROUND: To investigate the effect of COX-2 polymorphism and its product, prostaglandin E2 (PGE2), on stroke risk in an endemic area for Chagas disease. In a separate cohort, to investigate the effect of COX-2 polymorphisms on the total burden of cerebral white matter disease. METHODS: Cases were outpatients with ischemic stroke; controls were stroke-free subjects from 2 outpatient clinics (heart failure and caregivers of a movement disorders clinic). We extracted DNA from total blood to investigate the rs20417 COX-2 polymorphism. Serologic tests (Enzime-linked immunosorbent assay) were performed to confirm Trypanosoma cruzi infection and to quantify PGE2 levels. In the Boston cohort, white matter hyperintensity volume (WMHv) was quantified on the admission brain magnetic resonance images of subjects with ischemic stroke, who also donated DNA for the COX-2 gene region analysis. RESULTS: We studied 44 patients with stroke and 96 controls (46 with heart failure and 50 caregivers) in the Brazilian cohort; and 788 stroke patients (302 cardioembolic and 486 noncardioembolic) in the Boston cohort. In the Brazilian cohort, rs20417 polymorphism was associated with both stroke (P = 5 × 10(-6)) and decreased PGE2 levels (P = 4 × 10(-5)); similarly, Chagas was associated with stroke (P = 4 × 10(-3)) and decreased PGE2 levels (P = 7 × 10(-3)). In the Boston cohort, rs20417 polymorphism was associated with increased WMHv among noncardioembolic (P = .037), but not among cardioembolic stroke patients. CONCLUSIONS: Variation in COX-2 gene is associated with both symptomatic and silent brain cerebrovascular disease. This candidate gene region should be tested in population-based samples.
BACKGROUND: To investigate the effect of COX-2 polymorphism and its product, prostaglandin E2 (PGE2), on stroke risk in an endemic area for Chagas disease. In a separate cohort, to investigate the effect of COX-2 polymorphisms on the total burden of cerebral white matter disease. METHODS: Cases were outpatients with ischemic stroke; controls were stroke-free subjects from 2 outpatient clinics (heart failure and caregivers of a movement disorders clinic). We extracted DNA from total blood to investigate the rs20417COX-2 polymorphism. Serologic tests (Enzime-linked immunosorbent assay) were performed to confirm Trypanosoma cruzi infection and to quantify PGE2 levels. In the Boston cohort, white matter hyperintensity volume (WMHv) was quantified on the admission brain magnetic resonance images of subjects with ischemic stroke, who also donated DNA for the COX-2 gene region analysis. RESULTS: We studied 44 patients with stroke and 96 controls (46 with heart failure and 50 caregivers) in the Brazilian cohort; and 788 strokepatients (302 cardioembolic and 486 noncardioembolic) in the Boston cohort. In the Brazilian cohort, rs20417 polymorphism was associated with both stroke (P = 5 × 10(-6)) and decreased PGE2 levels (P = 4 × 10(-5)); similarly, Chagas was associated with stroke (P = 4 × 10(-3)) and decreased PGE2 levels (P = 7 × 10(-3)). In the Boston cohort, rs20417 polymorphism was associated with increased WMHv among noncardioembolic (P = .037), but not among cardioembolic strokepatients. CONCLUSIONS: Variation in COX-2 gene is associated with both symptomatic and silent brain cerebrovascular disease. This candidate gene region should be tested in population-based samples.
Authors: N S Rost; R M Rahman; A Biffi; E E Smith; A Kanakis; K Fitzpatrick; F Lima; B B Worrall; J F Meschia; R D Brown; T G Brott; A G Sorensen; S M Greenberg; K L Furie; J Rosand Journal: Neurology Date: 2010-11-09 Impact factor: 9.910
Authors: Jun Li; Xibin Liang; Qian Wang; Richard M Breyer; Louise McCullough; Katrin Andreasson Journal: Neurosci Lett Date: 2008-04-20 Impact factor: 3.046
Authors: Poneh Adib-Samii; Natalia Rost; Matthew Traylor; William Devan; Alessandro Biffi; Silvia Lanfranconi; Kaitlin Fitzpatrick; Steve Bevan; Allison Kanakis; Valerie Valant; Andreas Gschwendtner; Rainer Malik; Alexa Richie; Dale Gamble; Helen Segal; Eugenio A Parati; Emilio Ciusani; Elizabeth G Holliday; Jane Maguire; Joanna Wardlaw; Bradford Worrall; Joshua Bis; Kerri L Wiggins; Will Longstreth; Steve J Kittner; Yu-Ching Cheng; Thomas Mosley; Guido J Falcone; Karen L Furie; Carlos Leiva-Salinas; Benison C Lau; Muhammed Saleem Khan; Pankaj Sharma; Myriam Fornage; Braxton D Mitchell; Bruce M Psaty; Cathie Sudlow; Christopher Levi; Giorgio B Boncoraglio; Peter M Rothwell; James Meschia; Martin Dichgans; Jonathan Rosand; Hugh S Markus Journal: Stroke Date: 2013-05-14 Impact factor: 7.914