{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:59:49Z","timestamp":1791226789526,"version":"4.1.0"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose\u2014<\/jats:title>\n                    <jats:p>Elevated total plasma homocysteine (tHcy) levels are known to be associated with increased risk of ischemic stroke (IS). Given that both tHcy and IS are heritable traits, we investigated a potential genetic relationship between homocysteine levels and stroke risk by assessing 18 polymorphisms previously associated with tHcy levels for their association with IS and its subtypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods\u2014<\/jats:title>\n                    <jats:p>Previous meta-analysis results from an international stroke collaborative network, METASTROKE, were used to assess association of the 18 tHcy-associated single-nucleotide polymorphisms (SNPs) in 12 389 IS cases and 62 004 controls. We also investigated the associations in regions located within 50 kb from the 18 tHcy-related SNPs and the association of a genetic risk score, including the 18 SNPs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results\u2014<\/jats:title>\n                    <jats:p>\n                      One SNP located in the\n                      <jats:italic>RASIP1<\/jats:italic>\n                      gene and a cluster of 3 SNPs located at and near\n                      <jats:italic>SLC17A3<\/jats:italic>\n                      were significantly associated with IS (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.0003) after correcting for multiple testing. For stroke subtypes, the sentinel SNP located upstream of\n                      <jats:italic>MUT<\/jats:italic>\n                      was significantly associated with small-vessel disease (\n                      <jats:italic>P<\/jats:italic>\n                      =0.0022), whereas 1 SNP located in\n                      <jats:italic>MTHFR<\/jats:italic>\n                      was significantly associated with large-vessel disease (\n                      <jats:italic>P<\/jats:italic>\n                      =0.00019). A genetic risk score, including the 18 SNPs, did not show significant association with IS or its subtypes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\u2014<\/jats:title>\n                    <jats:p>\n                      This study found several potential associations with IS and its subtypes: an association of an\n                      <jats:italic>MUT<\/jats:italic>\n                      variant with small-vessel disease, an\n                      <jats:italic>MTHFR<\/jats:italic>\n                      variant with large-vessel disease, and associations of\n                      <jats:italic>RASIP1<\/jats:italic>\n                      and\n                      <jats:italic>SLC17A3<\/jats:italic>\n                      variants with overall IS.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/strokeaha.114.005208","type":"journal-article","created":{"date-parts":[[2014,5,21]],"date-time":"2014-05-21T00:43:17Z","timestamp":1400632997000},"page":"1920-1924","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":32,"title":["Effect of Genetic Variants Associated With Plasma Homocysteine Levels on Stroke Risk"],"prefix":"10.1161","volume":"45","author":[{"given":"Ioana","family":"Cotlarciuc","sequence":"first","affiliation":[{"name":"From the Department of Medicine, Imperial College Cerebrovascular Research Unit, Imperial College London, London, United Kingdom (I.C., N.H., P.E.R., P.S.); Institute for Stroke and Dementia Research, Medical Centre, Klinikum der Universit\u00e4t M\u00fcnchen, Ludwig-Maximilians-University, Munich, Germany (R.M., M.D.); Center for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia (E.G.H.); Department of Nutritional..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer","family":"Malik","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Imperial College Cerebrovascular Research Unit, Imperial College London, London, United Kingdom (I.C., N.H., P.E.R., P.S.); Institute for Stroke and Dementia Research, Medical Centre, Klinikum der Universit\u00e4t M\u00fcnchen, Ludwig-Maximilians-University, Munich, Germany (R.M., M.D.); Center for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia (E.G.H.); Department of Nutritional..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth G.","family":"Holliday","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Imperial College Cerebrovascular Research Unit, Imperial College London, London, United Kingdom (I.C., N.H., P.E.R., P.S.); Institute for Stroke and Dementia Research, Medical Centre, Klinikum der Universit\u00e4t M\u00fcnchen, Ludwig-Maximilians-University, Munich, Germany (R.M., M.D.); Center for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia (E.G.H.); Department of Nutritional..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kourosh R.","family":"Ahmadi","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Imperial College Cerebrovascular Research Unit, Imperial College London, London, United Kingdom (I.C., N.H., P.E.R., P.S.); Institute for Stroke and Dementia Research, Medical Centre, Klinikum der Universit\u00e4t M\u00fcnchen, Ludwig-Maximilians-University, Munich, Germany (R.M., M.D.); Center for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia (E.G.H.); Department of Nutritional..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Par\u00e9","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Imperial College Cerebrovascular Research Unit, Imperial College London, London, United Kingdom (I.C., N.H., P.E.R., P.S.); Institute for Stroke and Dementia Research, Medical Centre, Klinikum der Universit\u00e4t M\u00fcnchen, Ludwig-Maximilians-University, Munich, Germany (R.M., M.D.); Center for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia (E.G.H.); Department of Nutritional..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce M.","family":"Psaty","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Imperial College Cerebrovascular Research Unit, Imperial College London, London, United Kingdom (I.C., N.H., P.E.R., P.S.); Institute for Stroke and Dementia Research, Medical Centre, Klinikum der Universit\u00e4t M\u00fcnchen, Ludwig-Maximilians-University, Munich, Germany (R.M., M.D.); Center for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia (E.G.H.); Department of Nutritional..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Fornage","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Imperial College Cerebrovascular Research Unit, Imperial College London, London, United Kingdom (I.C., N.H., P.E.R., P.S.); Institute for Stroke and Dementia Research, Medical Centre, Klinikum der Universit\u00e4t M\u00fcnchen, Ludwig-Maximilians-University, Munich, Germany (R.M., M.D.); Center for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia (E.G.H.); Department of Nutritional..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazeeha","family":"Hasan","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Imperial College Cerebrovascular Research Unit, Imperial College London, London, United Kingdom (I.C., N.H., P.E.R., P.S.); Institute for Stroke and Dementia Research, Medical Centre, Klinikum der Universit\u00e4t M\u00fcnchen, Ludwig-Maximilians-University, Munich, Germany (R.M., M.D.); Center for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia (E.G.H.); Department of Nutritional..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul E.","family":"Rinne","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Imperial College Cerebrovascular Research Unit, Imperial College London, London, United Kingdom (I.C., N.H., P.E.R., P.S.); Institute for Stroke and Dementia Research, Medical Centre, Klinikum der Universit\u00e4t M\u00fcnchen, Ludwig-Maximilians-University, Munich, Germany (R.M., M.D.); Center for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia (E.G.H.); Department of Nutritional..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Arfan","family":"Ikram","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Imperial College Cerebrovascular Research Unit, Imperial College London, London, United Kingdom (I.C., N.H., P.E.R., P.S.); Institute for Stroke and Dementia Research, Medical Centre, Klinikum der Universit\u00e4t M\u00fcnchen, Ludwig-Maximilians-University, Munich, Germany (R.M., M.D.); Center for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia (E.G.H.); Department of Nutritional..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugh S.","family":"Markus","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Imperial College Cerebrovascular Research Unit, Imperial College London, London, United Kingdom (I.C., N.H., P.E.R., P.S.); Institute for Stroke and Dementia Research, Medical Centre, Klinikum der Universit\u00e4t M\u00fcnchen, Ludwig-Maximilians-University, Munich, Germany (R.M., M.D.); Center for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia (E.G.H.); Department of Nutritional..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Rosand","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Imperial College Cerebrovascular Research Unit, Imperial College London, London, United Kingdom (I.C., N.H., P.E.R., P.S.); Institute for Stroke and Dementia Research, Medical Centre, Klinikum der Universit\u00e4t M\u00fcnchen, Ludwig-Maximilians-University, Munich, Germany (R.M., M.D.); Center for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia (E.G.H.); Department of Nutritional..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Braxton D.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Imperial College Cerebrovascular Research Unit, Imperial College London, London, United Kingdom (I.C., N.H., P.E.R., P.S.); Institute for Stroke and Dementia Research, Medical Centre, Klinikum der Universit\u00e4t M\u00fcnchen, Ludwig-Maximilians-University, Munich, Germany (R.M., M.D.); Center for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia (E.G.H.); Department of Nutritional..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J.","family":"Kittner","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Imperial College Cerebrovascular Research Unit, Imperial College London, London, United Kingdom (I.C., N.H., P.E.R., P.S.); Institute for Stroke and Dementia Research, Medical Centre, Klinikum der Universit\u00e4t M\u00fcnchen, Ludwig-Maximilians-University, Munich, Germany (R.M., M.D.); Center for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia (E.G.H.); Department of Nutritional..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James F.","family":"Meschia","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Imperial College Cerebrovascular Research Unit, Imperial College London, London, United Kingdom (I.C., N.H., P.E.R., P.S.); Institute for Stroke and Dementia Research, Medical Centre, Klinikum der Universit\u00e4t M\u00fcnchen, Ludwig-Maximilians-University, Munich, Germany (R.M., M.D.); Center for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia (E.G.H.); Department of Nutritional..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce B.J.","family":"van 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Ludwig-Maximilians-University, Munich, Germany (R.M., M.D.); Center for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia (E.G.H.); Department of Nutritional..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradford B.","family":"Worrall","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Imperial College Cerebrovascular Research Unit, Imperial College London, London, United Kingdom (I.C., N.H., P.E.R., P.S.); Institute for Stroke and Dementia Research, Medical Centre, Klinikum der Universit\u00e4t M\u00fcnchen, Ludwig-Maximilians-University, Munich, Germany (R.M., M.D.); Center for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia (E.G.H.); Department of 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