Abstract
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. 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. MTHFR C677T was associated with lacunar stroke (P=0....Continue Reading
References
Jun 22, 1991·Lancet·J BamfordC Warlow
Jan 1, 1993·Stroke; a Journal of Cerebral Circulation·H P AdamsE E Marsh
Oct 26, 2002·JAMA : the Journal of the American Medical Association·UNKNOWN Homocysteine Studies Collaboration
Nov 11, 2003·Brain : a Journal of Neurology·Ahamad HassanHugh S Markus
Feb 6, 2004·Stroke; a Journal of Cerebral Circulation·Frank M Faraci, Steven R Lentz
Feb 6, 2004·JAMA : the Journal of the American Medical Association·James F TooleMeir Stampfer
May 26, 2004·Circulation·Hiroyasu IsoTakashi Shimamoto
Mar 15, 2006·The New England Journal of Medicine·Eva LonnUNKNOWN Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators
Jul 25, 2006·Nature Genetics·Alkes L PriceDavid Reich
Jan 24, 2007·Lancet Neurology·Martin Dichgans
Oct 31, 2007·Circulation·Hugh S MarkusPaula Jerrard-Dunne
Sep 2, 2008·Stroke; a Journal of Cerebral Circulation·Usman KhanHugh S Markus
May 2, 2009·Stroke; a Journal of Cerebral Circulation·Lavinia PaternosterCathie L M Sudlow
Jun 24, 2010·JAMA : the Journal of the American Medical Association·UNKNOWN Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative GroupRory Collins
Aug 7, 2010·Lancet Neurology·UNKNOWN VITATOPS Trial Study Group
Aug 2, 2011·Lancet·Michael V HolmesJuan P Casas
Oct 25, 2012·Stroke; a Journal of Cerebral Circulation·Margherita CavalieriUNKNOWN VITATOPS Trial Study Group
Nov 7, 2012·Nature·UNKNOWN 1000 Genomes Project ConsortiumGil A McVean
May 16, 2013·Stroke; a Journal of Cerebral Circulation·Poneh Adib-SamiiUNKNOWN International Stroke Genetics Consortium
Jul 5, 2013·The American Journal of Clinical Nutrition·Joyce B J van MeursKourosh R Ahmadi
Jul 23, 2013·Lancet Neurology·Joanna M WardlawUNKNOWN STandards for ReportIng Vascular changes on nEuroimaging (STRIVE v1)
May 23, 2014·Stroke; a Journal of Cerebral Circulation·Ioana CotlarciucUNKNOWN METASTROKE and the International Stroke Genetics Consortium
Mar 17, 2015·JAMA : the Journal of the American Medical Association·Yong HuoUNKNOWN CSPPT Investigators
Citations
Sep 1, 2018·JAMA Neurology·Robert W RegenhardtLouis R Caplan
Jan 9, 2019·Annals of the New York Academy of Sciences·Loes C A Rutten-Jacobs, Natalia S Rost
Jan 22, 2019·Stroke; a Journal of Cerebral Circulation·Hugh S Markus, Reinhold Schmidt
Feb 21, 2019·Annals of Neurology·Susanna C LarssonHugh S Markus
Mar 19, 2019·International Journal of Immunogenetics·Arezou SayadSoudeh Ghafouri-Fard
Feb 18, 2017·Nature Reviews. Neurology·Vincent C T MokLawrence K S Wong
Feb 24, 2019·Neurology·Martin SöderholmUNKNOWN International Stroke Genetics Consortium, the NINDS-SiGN Consortium, and the Genetics of Ischaemic Stroke Functional Outcome
May 23, 2020·Current Atherosclerosis Reports·Minghua Liu, Jose Gutierrez
Sep 6, 2018·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Christoph J GriessenauerClemens M Schirmer
Feb 6, 2018·Journal of Clinical Laboratory Analysis·Koroush KhalighiWuqiang Fan
Jan 29, 2019·Frontiers in Neurology·Xin ZhangRui Li
Aug 16, 2016·Molecular Nutrition & Food Research·Qiang ZengHang Xiang
Feb 27, 2020·The International Journal of Neuroscience·Mehrdokht MazdehSoudeh Ghafouri-Fard
Mar 3, 2020·PeerJ·Hongyu YuanXiaoyan Ren
Feb 13, 2018·Medicina·In Wook HwangHan Jun Jin
Jul 30, 2020·Brain Sciences·Dana Simona ChitaSimona Ruxanda Dragan
Jul 1, 2019·Clinical Neurology and Neurosurgery·Marina Yurievna MaksimovaAslan Amirkhanovich Kubatiev
Aug 3, 2019·Journal of the Neurological Sciences·Yifan JiYanhong Dong
Dec 2, 2020·Journal of Stroke and Cerebrovascular Diseases : the Official Journal of National Stroke Association·Yifan JiPei Yuan Lv
Dec 31, 2020·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·Yuze CaoJun Ni
Nov 10, 2020·Heliyon·Ádám AnnusPéter Klivényi
Mar 7, 2021·International Journal of Molecular Sciences·Rita MorettiClaudio Tiribelli
Apr 20, 2021·Frontiers in Genetics·Weishi LiuYuming Xu