title: COX-2 rs20417 Polymorphism Is Associated with Stroke and White Matter Disease.
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.
authors.affiliation: 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.
authors.forename: Jamary
authors.initials: J
authors.lastname: Oliveira-Filho
authors.affiliation: 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.
authors.forename: Ana C P
authors.initials: AC
authors.lastname: Ornellas
authors.affiliation: Stroke Division, Massachusetts General Hospital, Boston, USA.
authors.forename: Cathy R
authors.initials: CR
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Luciana M B
authors.initials: LM
authors.lastname: Oliveira
authors.affiliation: Universidade Federal do Oeste da Bahia (UFOB), Barreiras, Brazil.
authors.forename: Théo
authors.initials: T
authors.lastname: Araújo-Santos
authors.affiliation: Centro de Pesquisas Goncalo Moniz, Oswaldo Cruz Foundation-Bahia (CPqGM, FIOCRUZ-BA), Salvador, Brazil.
authors.forename: Valeria M
authors.initials: VM
authors.lastname: Borges
authors.affiliation: 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.
authors.forename: Laís M G B
authors.initials: LM
authors.lastname: Ventura
authors.affiliation: Stroke and Cardiomyopathy Clinics, Federal University of Bahia, Salvador, Brazil.
authors.forename: Francisco J F B
authors.initials: FJ
authors.lastname: Reis
authors.affiliation: Stroke and Cardiomyopathy Clinics, Federal University of Bahia, Salvador, Brazil.
authors.forename: Roque
authors.initials: R
authors.lastname: Aras
authors.affiliation: Stroke and Cardiomyopathy Clinics, Federal University of Bahia, Salvador, Brazil.
authors.forename: André M
authors.initials: AM
authors.lastname: Fernandes
authors.affiliation: Stroke Division, Massachusetts General Hospital, Boston, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rosand
authors.affiliation: Stroke Division, Massachusetts General Hospital, Boston, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Greenberg
authors.affiliation: Department of Neurology, Brown University, Providence, USA.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Furie
authors.affiliation: Stroke Division, Massachusetts General Hospital, Boston, USA.
authors.forename: Natalia S
authors.initials: NS
authors.lastname: Rost
mesh_terms: D000368:Aged; D017028:Caregivers / Q000523:psychology; D015331:Cohort Studies; D051546:Cyclooxygenase 2 / Q000235:genetics*; D015232:Dinoprostone / Q000097:blood; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D056784:Leukoencephalopathies / Q000097:blood / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D020521:Stroke / Q000097:blood / Q000235:genetics*
chemical_list: D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone
keywords: Acute cerebral infarction; Chagas disease; cyclooxygenase; genetics of stroke; magnetic resonance imaging; prostaglandin E2