Your browser doesn't support javascript.
loading
PATJ Low Frequency Variants Are Associated With Worse Ischemic Stroke Functional Outcome.
Mola-Caminal, Marina; Carrera, Caty; Soriano-Tárraga, Carolina; Giralt-Steinhauer, Eva; Díaz-Navarro, Rosa M; Tur, Sílvia; Jiménez, Carmen; Medina-Dols, Aina; Cullell, Natàlia; Torres-Aguila, Nuria P; Muiño, Elena; Rodríguez-Campello, Ana; Ois, Angel; Cuadrado-Godia, Elisa; Vivanco-Hidalgo, Rosa M; Hernandez-Guillamon, Mar; Solé, Montse; Delgado, Pilar; Bustamante, Alejandro; García-Berrocoso, Teresa; Mendióroz, Maite; Castellanos, Mar; Serena, Joaquín; Martí-Fàbregas, Joan; Segura, Tomás; Serrano-Heras, Gemma; Obach, Victor; Ribó, Marc; Molina, Carlos A; Alvarez-Sabín, José; Palomeras, Ernest; Freijo, Mar; Font, Maria A; Rosand, Jonathan; Rost, Natalia S; Gallego-Fabrega, Cristina; Lee, Jin-Moo; Heitsch, Laura; Ibanez, Laura; Cruchaga, Carlos; Phuah, Chia-Ling; Lemmens, Robin; Thijs, Vincent; Lindgren, Arne; Maguire, Jane; Rannikmae, Kristiina; Sudlow, Catherine L; Jern, Christina; Stanne, Tara M; Lorentzen, Erik.
Afiliação
  • Mola-Caminal M; From the Department of Neurology, Neurovascular Research Group, Hospital del Mar Medical Research Institute, Universitat Autònoma de Barcelona/DCEXS-Universitat Pompeu Fabra (M.M.-C., C.S.-T., E.G.-S., A.R.-C., A.O., E.C.-G., R.M.V.-H., J.R., J.J.-C.).
  • Carrera C; Department of Genetics, Universitat de Barcelona (M.M.-C.).
  • Soriano-Tárraga C; Neurovascular Research Laboratory, Vall d'Hebron Institute of Research (C.C., M.H.-G., M.S., P.D., A.B., T.G.-B., M.M., J.M., I.F.-C.), Universitat Autònoma de Barcelona.
  • Giralt-Steinhauer E; From the Department of Neurology, Neurovascular Research Group, Hospital del Mar Medical Research Institute, Universitat Autònoma de Barcelona/DCEXS-Universitat Pompeu Fabra (M.M.-C., C.S.-T., E.G.-S., A.R.-C., A.O., E.C.-G., R.M.V.-H., J.R., J.J.-C.).
  • Díaz-Navarro RM; From the Department of Neurology, Neurovascular Research Group, Hospital del Mar Medical Research Institute, Universitat Autònoma de Barcelona/DCEXS-Universitat Pompeu Fabra (M.M.-C., C.S.-T., E.G.-S., A.R.-C., A.O., E.C.-G., R.M.V.-H., J.R., J.J.-C.).
  • Tur S; Department of Neurology (R.M.D.-N., S.T., C.J.), Son Espases University Hospital, Institut d'Investigació Sanitària de Les Illes Balears, Palma de Mallorca.
  • Jiménez C; Department of Neurology (R.M.D.-N., S.T., C.J.), Son Espases University Hospital, Institut d'Investigació Sanitària de Les Illes Balears, Palma de Mallorca.
  • Medina-Dols A; Department of Neurology (R.M.D.-N., S.T., C.J.), Son Espases University Hospital, Institut d'Investigació Sanitària de Les Illes Balears, Palma de Mallorca.
  • Cullell N; Research Unit (A.M.-D., C.V.-B.), Son Espases University Hospital, Institut d'Investigació Sanitària de Les Illes Balears, Palma de Mallorca.
  • Torres-Aguila NP; Stroke Pharmacogenomics and Genetics Group, Fundació Docència i Recerca Mútua Terrassa (N.C., N.P.T.-A., E.M., I.F.-C.).
  • Muiño E; Stroke Pharmacogenomics and Genetics Group, Fundació Docència i Recerca Mútua Terrassa (N.C., N.P.T.-A., E.M., I.F.-C.).
  • Rodríguez-Campello A; Stroke Pharmacogenomics and Genetics Group, Fundació Docència i Recerca Mútua Terrassa (N.C., N.P.T.-A., E.M., I.F.-C.).
  • Ois A; From the Department of Neurology, Neurovascular Research Group, Hospital del Mar Medical Research Institute, Universitat Autònoma de Barcelona/DCEXS-Universitat Pompeu Fabra (M.M.-C., C.S.-T., E.G.-S., A.R.-C., A.O., E.C.-G., R.M.V.-H., J.R., J.J.-C.).
  • Cuadrado-Godia E; From the Department of Neurology, Neurovascular Research Group, Hospital del Mar Medical Research Institute, Universitat Autònoma de Barcelona/DCEXS-Universitat Pompeu Fabra (M.M.-C., C.S.-T., E.G.-S., A.R.-C., A.O., E.C.-G., R.M.V.-H., J.R., J.J.-C.).
  • Vivanco-Hidalgo RM; From the Department of Neurology, Neurovascular Research Group, Hospital del Mar Medical Research Institute, Universitat Autònoma de Barcelona/DCEXS-Universitat Pompeu Fabra (M.M.-C., C.S.-T., E.G.-S., A.R.-C., A.O., E.C.-G., R.M.V.-H., J.R., J.J.-C.).
  • Hernandez-Guillamon M; From the Department of Neurology, Neurovascular Research Group, Hospital del Mar Medical Research Institute, Universitat Autònoma de Barcelona/DCEXS-Universitat Pompeu Fabra (M.M.-C., C.S.-T., E.G.-S., A.R.-C., A.O., E.C.-G., R.M.V.-H., J.R., J.J.-C.).
  • Solé M; Neurovascular Research Laboratory, Vall d'Hebron Institute of Research (C.C., M.H.-G., M.S., P.D., A.B., T.G.-B., M.M., J.M., I.F.-C.), Universitat Autònoma de Barcelona.
  • Delgado P; Neurovascular Research Laboratory, Vall d'Hebron Institute of Research (C.C., M.H.-G., M.S., P.D., A.B., T.G.-B., M.M., J.M., I.F.-C.), Universitat Autònoma de Barcelona.
  • Bustamante A; Neurovascular Research Laboratory, Vall d'Hebron Institute of Research (C.C., M.H.-G., M.S., P.D., A.B., T.G.-B., M.M., J.M., I.F.-C.), Universitat Autònoma de Barcelona.
  • García-Berrocoso T; Neurovascular Research Laboratory, Vall d'Hebron Institute of Research (C.C., M.H.-G., M.S., P.D., A.B., T.G.-B., M.M., J.M., I.F.-C.), Universitat Autònoma de Barcelona.
  • Mendióroz M; Neurovascular Research Laboratory, Vall d'Hebron Institute of Research (C.C., M.H.-G., M.S., P.D., A.B., T.G.-B., M.M., J.M., I.F.-C.), Universitat Autònoma de Barcelona.
  • Castellanos M; Neurovascular Research Laboratory, Vall d'Hebron Institute of Research (C.C., M.H.-G., M.S., P.D., A.B., T.G.-B., M.M., J.M., I.F.-C.), Universitat Autònoma de Barcelona.
  • Serena J; Neurology Service, A Coruña University Hospital and Biomedical Research Institute, La Coruña (M.C.).
  • Martí-Fàbregas J; Department of Neurology, Doctor Josep Trueta University Hospital, Girona Institute of Biomedical Investigation (J.S.).
  • Segura T; Stroke Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona (J.M.-F.S.).
  • Serrano-Heras G; Department of Neurology (T.S.), Complejo Hospitalario Universitario de Albacete.
  • Obach V; Research Unit (G.S.-H.), Complejo Hospitalario Universitario de Albacete.
  • Ribó M; Department of Neurology, Hospital Clínic i Provincial de Barcelona (V.O.).
  • Molina CA; Stroke Unit, Department of Neurology, Hospital Universitari Vall d'Hebron, Barcelona (M.R., C.A.M., J.A.-S.).
  • Alvarez-Sabín J; Stroke Unit, Department of Neurology, Hospital Universitari Vall d'Hebron, Barcelona (M.R., C.A.M., J.A.-S.).
  • Palomeras E; Stroke Unit, Department of Neurology, Hospital Universitari Vall d'Hebron, Barcelona (M.R., C.A.M., J.A.-S.).
  • Freijo M; Department of Neurology, Hospital de Mataró (E.P.).
  • Font MA; Department of Neurology, Hospital de Basurto, Bilbao (M.F.).
  • Rosand J; Department of Neurology, Hospital de Bellvitge, Hospitalet de Llobregat (M.A.F.).
  • Rost NS; From the Department of Neurology, Neurovascular Research Group, Hospital del Mar Medical Research Institute, Universitat Autònoma de Barcelona/DCEXS-Universitat Pompeu Fabra (M.M.-C., C.S.-T., E.G.-S., A.R.-C., A.O., E.C.-G., R.M.V.-H., J.R., J.J.-C.).
  • Gallego-Fabrega C; Department of Neurology, J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School, Boston (J.R., N.S.R.).
  • Lee JM; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA (J.R., C.G.-F.).
  • Heitsch L; Center for Genomic Medicine, Massachusetts General Hospital, Boston (J.R., C.G.F.).
  • Ibanez L; Department of Neurology (J.-M.L., L.H., L.I., C.C., C.-L.P.), Washington University School of Medicine, St. Louis, MO.
  • Cruchaga C; Department of Neurology (J.-M.L., L.H., L.I., C.C., C.-L.P.), Washington University School of Medicine, St. Louis, MO.
  • Phuah CL; The Division of Emergency Medicine (L.H.), Washington University School of Medicine, St. Louis, MO.
  • Lemmens R; Department of Neurology (J.-M.L., L.H., L.I., C.C., C.-L.P.), Washington University School of Medicine, St. Louis, MO.
  • Thijs V; Department of Neurology (J.-M.L., L.H., L.I., C.C., C.-L.P.), Washington University School of Medicine, St. Louis, MO.
  • Lindgren A; Department of Neurology (J.-M.L., L.H., L.I., C.C., C.-L.P.), Washington University School of Medicine, St. Louis, MO.
  • Maguire J; Department of Neurosciences, Experimental Neurology, KU Leuven - University of Leuven, Belgium (R.L.).
  • Rannikmae K; Laboratory of Neurobiology, VIB, Center for Brain & Disease Research, Leuven (R.L.).
  • Sudlow CL; Department of Neurology, University Hospitals Leuven (R.L.).
  • Jern C; Stroke Division, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Heidelberg, Australia (V.T.).
  • Stanne TM; Department of Neurology, Austin Health, Heidelberg, Australia (V.T.).
  • Lorentzen E; Clinical Sciences Lund, Neurology, Lund University, Sweden (A.L.).
Circ Res ; 124(1): 114-120, 2019 01 04.
Article em En | MEDLINE | ID: mdl-30582445
ABSTRACT
RATIONALE Ischemic stroke is among the leading causes of adult disability. Part of the variability in functional outcome after stroke has been attributed to genetic factors but no locus has been consistently associated with stroke outcome.

OBJECTIVE:

Our aim was to identify genetic loci influencing the recovery process using accurate phenotyping to produce the largest GWAS (genome-wide association study) in ischemic stroke recovery to date. METHODS AND

RESULTS:

A 12-cohort, 2-phase (discovery-replication and joint) meta-analysis of GWAS included anterior-territory and previously independent ischemic stroke cases. Functional outcome was recorded using 3-month modified Rankin Scale. Analyses were adjusted for confounders such as discharge National Institutes of Health Stroke Scale. A gene-based burden test was performed. The discovery phase (n=1225) was followed by open (n=2482) and stringent joint-analyses (n=1791). Those cohorts with modified Rankin Scale recorded at time points other than 3-month or incomplete data on previous functional status were excluded in the stringent analyses. Novel variants in PATJ (Pals1-associated tight junction) gene were associated with worse functional outcome at 3-month after stroke. The top variant was rs76221407 (G allele, ß=0.40, P=1.70×10-9).

CONCLUSIONS:

Our results identify a set of common variants in PATJ gene associated with 3-month functional outcome at genome-wide significance level. Future studies should examine the role of PATJ in stroke recovery and consider stringent phenotyping to enrich the information captured to unveil additional stroke outcome loci.
Assuntos
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Isquemia Encefálica / Acidente Vascular Cerebral / Polimorfismo de Nucleotídeo Único / Proteínas de Junções Íntimas Tipo de estudo: Diagnostic_studies / Etiology_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Humans Idioma: En Revista: Circ Res Ano de publicação: 2019 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Isquemia Encefálica / Acidente Vascular Cerebral / Polimorfismo de Nucleotídeo Único / Proteínas de Junções Íntimas Tipo de estudo: Diagnostic_studies / Etiology_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Humans Idioma: En Revista: Circ Res Ano de publicação: 2019 Tipo de documento: Article