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Association of MTHFR C677T Genotype With Ischemic Stroke Is Confined to Cerebral Small Vessel Disease Subtype.
Rutten-Jacobs, Loes C A; Traylor, Matthew; Adib-Samii, Poneh; Thijs, Vincent; Sudlow, Cathie; Rothwell, Peter M; Boncoraglio, Giorgio; Dichgans, Martin; Meschia, James; Maguire, Jane; Levi, Christopher; Rost, Natalia S; Rosand, Jonathan; Hassan, Ahamad; Bevan, Steve; Markus, Hugh S.
Afiliação
  • Rutten-Jacobs LC; From the Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK (L.C.A.R.-J., M.T., H.S.M.); Department of Medical & Molecular Genetics, King's College London, London, UK (M.T.); Stroke and Dementia Research Centre, Department of Clinical Neuroscience, St George's Universit
  • Traylor M; From the Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK (L.C.A.R.-J., M.T., H.S.M.); Department of Medical & Molecular Genetics, King's College London, London, UK (M.T.); Stroke and Dementia Research Centre, Department of Clinical Neuroscience, St George's Universit
  • Adib-Samii P; From the Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK (L.C.A.R.-J., M.T., H.S.M.); Department of Medical & Molecular Genetics, King's College London, London, UK (M.T.); Stroke and Dementia Research Centre, Department of Clinical Neuroscience, St George's Universit
  • Thijs V; From the Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK (L.C.A.R.-J., M.T., H.S.M.); Department of Medical & Molecular Genetics, King's College London, London, UK (M.T.); Stroke and Dementia Research Centre, Department of Clinical Neuroscience, St George's Universit
  • Sudlow C; From the Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK (L.C.A.R.-J., M.T., H.S.M.); Department of Medical & Molecular Genetics, King's College London, London, UK (M.T.); Stroke and Dementia Research Centre, Department of Clinical Neuroscience, St George's Universit
  • Rothwell PM; From the Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK (L.C.A.R.-J., M.T., H.S.M.); Department of Medical & Molecular Genetics, King's College London, London, UK (M.T.); Stroke and Dementia Research Centre, Department of Clinical Neuroscience, St George's Universit
  • Boncoraglio G; From the Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK (L.C.A.R.-J., M.T., H.S.M.); Department of Medical & Molecular Genetics, King's College London, London, UK (M.T.); Stroke and Dementia Research Centre, Department of Clinical Neuroscience, St George's Universit
  • Dichgans M; From the Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK (L.C.A.R.-J., M.T., H.S.M.); Department of Medical & Molecular Genetics, King's College London, London, UK (M.T.); Stroke and Dementia Research Centre, Department of Clinical Neuroscience, St George's Universit
  • Meschia J; From the Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK (L.C.A.R.-J., M.T., H.S.M.); Department of Medical & Molecular Genetics, King's College London, London, UK (M.T.); Stroke and Dementia Research Centre, Department of Clinical Neuroscience, St George's Universit
  • Maguire J; From the Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK (L.C.A.R.-J., M.T., H.S.M.); Department of Medical & Molecular Genetics, King's College London, London, UK (M.T.); Stroke and Dementia Research Centre, Department of Clinical Neuroscience, St George's Universit
  • Levi C; From the Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK (L.C.A.R.-J., M.T., H.S.M.); Department of Medical & Molecular Genetics, King's College London, London, UK (M.T.); Stroke and Dementia Research Centre, Department of Clinical Neuroscience, St George's Universit
  • Rost NS; From the Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK (L.C.A.R.-J., M.T., H.S.M.); Department of Medical & Molecular Genetics, King's College London, London, UK (M.T.); Stroke and Dementia Research Centre, Department of Clinical Neuroscience, St George's Universit
  • Rosand J; From the Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK (L.C.A.R.-J., M.T., H.S.M.); Department of Medical & Molecular Genetics, King's College London, London, UK (M.T.); Stroke and Dementia Research Centre, Department of Clinical Neuroscience, St George's Universit
  • Hassan A; From the Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK (L.C.A.R.-J., M.T., H.S.M.); Department of Medical & Molecular Genetics, King's College London, London, UK (M.T.); Stroke and Dementia Research Centre, Department of Clinical Neuroscience, St George's Universit
  • Bevan S; From the Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK (L.C.A.R.-J., M.T., H.S.M.); Department of Medical & Molecular Genetics, King's College London, London, UK (M.T.); Stroke and Dementia Research Centre, Department of Clinical Neuroscience, St George's Universit
  • Markus HS; From the Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK (L.C.A.R.-J., M.T., H.S.M.); Department of Medical & Molecular Genetics, King's College London, London, UK (M.T.); Stroke and Dementia Research Centre, Department of Clinical Neuroscience, St George's Universit
Stroke ; 47(3): 646-51, 2016 Mar.
Article em En | MEDLINE | ID: mdl-26839351
ABSTRACT
BACKGROUND AND

PURPOSE:

Elevated plasma homocysteine levels are associated with stroke. However, this might be a reflection of bias or confounding because trials have failed to demonstrate an effect from homocysteine lowering in stroke patients, although a possible benefit has been suggested in lacunar stroke. Genetic studies could potentially overcome these issues because genetic variants are inherited randomly and are fixed at conception. Therefore, we tested the homocysteine levels-associated genetic variant MTHFR C677T for association with magnetic resonance imaging-confirmed lacunar stroke and compared this with associations with large artery and cardioembolic stroke subtypes.

METHODS:

We included 1359 magnetic resonance imaging-confirmed lacunar stroke cases, 1824 large artery stroke cases, 1970 cardioembolic stroke cases, and 14 448 controls, all of European ancestry. Furthermore, we studied 3670 ischemic stroke patients in whom white matter hyperintensities volume was measured. We tested MTHFR C677T for association with stroke subtypes and white matter hyperintensities volume. Because of the established association of homocysteine with hypertension, we additionally stratified for hypertension status.

RESULTS:

MTHFR C677T was associated with lacunar stroke (P=0.0003) and white matter hyperintensity volume (P=0.04), but not with the other stroke subtypes. Stratifying the lacunar stroke cases for hypertension status confirmed this association in hypertensive individuals (P=0.0002), but not in normotensive individuals (P=0.30).

CONCLUSIONS:

MTHFR C677T was associated with magnetic resonance imaging-confirmed lacunar stroke, but not large artery or cardioembolic stroke. The association may act through increased susceptibility to, or interaction with, high blood pressure. This heterogeneity of association might explain the lack of effect of lowering homocysteine in secondary prevention trials which included all strokes.
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Isquemia Encefálica / Metilenotetra-Hidrofolato Redutase (NADPH2) / Estudos de Associação Genética / Doenças de Pequenos Vasos Cerebrais / Acidente Vascular Cerebral Lacunar / Genótipo Tipo de estudo: Diagnostic_studies / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Male Idioma: En Revista: Stroke Ano de publicação: 2016 Tipo de documento: Article
Texto completo
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Isquemia Encefálica / Metilenotetra-Hidrofolato Redutase (NADPH2) / Estudos de Associação Genética / Doenças de Pequenos Vasos Cerebrais / Acidente Vascular Cerebral Lacunar / Genótipo Tipo de estudo: Diagnostic_studies / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Male Idioma: En Revista: Stroke Ano de publicação: 2016 Tipo de documento: Article