Journal article

Association of MTHFR C677T Genotype With Ischemic Stroke Is Confined to Cerebral Small Vessel Disease Subtype

Loes CA Rutten-Jacobs, Matthew Traylor, Poneh Adib-Samii, Vincent Thijs, Cathie Sudlow, Peter M Rothwell, Giorgio Boncoraglio, Martin Dichgans, James Meschia, Jane Maguire, Christopher Levi, Natalia S Rost, Jonathan Rosand, Ahamad Hassan, Steve Bevan, Hugh S Markus



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: ..

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Awarded by Wellcome Trust

Awarded by Stroke Association

Awarded by National Institute of Neurological Disorders and Stroke

Awarded by Stroke Association/British Heart Foundation programme grant

Awarded by NHMRC

Awarded by National Institute of Neurological Disorders and Stroke grant

Awarded by Medical Research Council

Awarded by National Institute for Health Research

Funding Acknowledgements

Collection of the UK Young Lacunar Stroke DNA Study (DNA Lacunar) was primarily supported by the Wellcome Trust (WT072952) with additional support from the Stroke Association (TSA 2010/01). Genotyping of the DNA Lacunar samples and Dr Traylor were supported by a Stroke Association Grant (FSA 2013/00). Genotyping of WTCCC2 ischemic stroke study was funded by the Wellcome Trust. The Oxford Vascular Study has been funded by Wellcome Trust, Wolfson Foundation, UK Stroke Association, British Heart Foundation, Dunhill Medical Trust, National Institute of Health Research (NIHR), Medical Research Council, and the NIHR Oxford Biomedical Research Centre. Funding for the genotyping at Massachusetts General Hospital was provided by the Massachusetts General Hospital-Deane Institute for the Integrative Study of Atrial Fibrillation and Stroke and the National Institute of Neurological Disorders and Stroke (U01 NS069208). Dr Rutten-Jacobs was supported by a Stroke Association/British Heart Foundation programme grant (TSA BHF 2010/01). Dr Adib-Samii was supported by a Medical Research Council (United Kingdom) training fellowship. Drs Markus and Bevan are supported by the National Institute for Health Research Cambridge University Hospitals Comprehensive Biomedical Research Centre. Dr Markus is supported by a National Institute for Health Research Senior Investigator award. Dr Thijs is supported by a Clinical Investigator Grant from the scientific research fund, Fonds Wetenschappelijk Onderzoek Flanders. Dr Levi is supported by a National Health and Medical Research Council (NHMRC Australia) Practitioner Fellowship and the Australian Stroke Genetics Collaboration has received Project Grant support from the NHMRC (App 1010287). Dr Rost was supported by a National Institute of Neurological Disorders and Stroke grant (R01 NS082285-01). Professor Rothwell is in receipt of an NIHR Senior Investigator Award and a Wellcome Trust Senior Investigator Award. We. also acknowledge the use of the facilities of the Acute Vascular Imaging Centre, Oxford, and the Cardiovascular Clinical Research Facility, Oxford. The sponsors of the study had no role in the study design, data collection, data analysis, interpretation, writing of the article, or the decision to submit the article for publication.