{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,8]],"date-time":"2026-11-08T03:16:51Z","timestamp":1794107811724,"version":"4.8.0"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:sec>\n            <jats:title>Background and Purpose\u2014<\/jats:title>\n            <jats:p>Elevated blood homocysteine concentration increases the risk of stroke, especially among hypertensive individuals. Homocysteine is largely affected by the methylenetetrahydrofolate reductase C677T polymorphism and folate status. Among hypertensive patients, we aimed to test the hypothesis that the association between homocysteine and stroke can be modified by the methylenetetrahydrofolate reductase C677T polymorphism and folic acid intervention.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods\u2014<\/jats:title>\n            <jats:p>We analyzed the data of 20 424 hypertensive adults enrolled in the China Stroke Primary Prevention Trial. The participants, first stratified by methylenetetrahydrofolate reductase genotype, were randomly assigned to receive double-blind treatments of 10-mg enalapril and 0.8-mg folic acid or 10-mg enalapril only. The participants were followed up for a median of 4.5 years.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results\u2014<\/jats:title>\n            <jats:p>\n              In the control group, baseline log-transformed homocysteine was associated with an increased risk of first stroke among participants with the CC\/CT genotype (hazard ratio, 3.1; 1.1\u20139.2), but not among participants with the TT genotype (hazard ratio, 0.7; 0.2\u20132.1), indicating a significant gene\u2013homocysteine interaction (\n              <jats:italic>P<\/jats:italic>\n              =0.008). In the folic acid intervention group, homocysteine showed no significant effect on stroke regardless of genotype. Consistently, folic acid intervention significantly reduced stroke risk in participants with CC\/CT genotypes and high homocysteine levels (tertile 3; hazard ratio, 0.73; 0.55\u20130.97).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>In Chinese hypertensive patients, the effect of homocysteine on the first stroke was significantly modified by the methylenetetrahydrofolate reductase C677T genotype and folic acid supplementation. Such information may help to more precisely predict stroke risk and develop folic acid interventions tailored to individual genetic background and nutritional status.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Clinical Trial Registration\u2014<\/jats:title>\n            <jats:p>\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.clinicaltrials.gov\">http:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              . Unique identifier: NCT00794885.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.116.015324","type":"journal-article","created":{"date-parts":[[2017,3,31]],"date-time":"2017-03-31T01:04:39Z","timestamp":1490922279000},"page":"1183-1190","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":104,"title":["Homocysteine and Stroke Risk"],"prefix":"10.1161","volume":"48","author":[{"given":"Min","family":"Zhao","sequence":"first","affiliation":[{"name":"From the National Clinical Research Study Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (M.Z., X.Q., B.W., F.F.H.); Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD (X.W.); Department of Neurology, First People\u2019s Hospital, Lianyungang, China (M.H.); Institute for Biomedicine, Anhui Medical University, Hefei,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobin","family":"Wang","sequence":"additional","affiliation":[{"name":"From the National Clinical Research Study Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (M.Z., X.Q., B.W., F.F.H.); Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD (X.W.); Department of Neurology, First People\u2019s Hospital, Lianyungang, China (M.H.); Institute for Biomedicine, Anhui Medical University, Hefei,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingli","family":"He","sequence":"additional","affiliation":[{"name":"From the National Clinical Research Study Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (M.Z., X.Q., B.W., F.F.H.); Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD (X.W.); Department of Neurology, First People\u2019s Hospital, Lianyungang, China (M.H.); Institute for Biomedicine, Anhui Medical University, Hefei,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianhui","family":"Qin","sequence":"additional","affiliation":[{"name":"From the National Clinical Research Study Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (M.Z., X.Q., B.W., F.F.H.); Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD (X.W.); Department of Neurology, First People\u2019s Hospital, Lianyungang, China (M.H.); Institute for Biomedicine, Anhui Medical University, Hefei,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genfu","family":"Tang","sequence":"additional","affiliation":[{"name":"From the National Clinical Research Study Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (M.Z., X.Q., B.W., F.F.H.); Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD (X.W.); Department of Neurology, First People\u2019s Hospital, Lianyungang, China (M.H.); Institute for Biomedicine, Anhui Medical University, Hefei,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Huo","sequence":"additional","affiliation":[{"name":"From the National Clinical Research Study Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (M.Z., X.Q., B.W., F.F.H.); Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD (X.W.); Department of Neurology, First People\u2019s Hospital, Lianyungang, China (M.H.); Institute for Biomedicine, Anhui Medical University, Hefei,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianping","family":"Li","sequence":"additional","affiliation":[{"name":"From the National Clinical Research Study Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (M.Z., X.Q., B.W., F.F.H.); Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD (X.W.); Department of Neurology, First People\u2019s Hospital, Lianyungang, China (M.H.); Institute for Biomedicine, Anhui Medical University, Hefei,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Fu","sequence":"additional","affiliation":[{"name":"From the National Clinical Research Study Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (M.Z., X.Q., B.W., F.F.H.); Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD (X.W.); Department of Neurology, First People\u2019s Hospital, Lianyungang, China (M.H.); Institute for Biomedicine, Anhui Medical University, Hefei,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Huang","sequence":"additional","affiliation":[{"name":"From the National Clinical Research Study Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (M.Z., X.Q., B.W., F.F.H.); Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD (X.W.); Department of Neurology, First People\u2019s Hospital, Lianyungang, China (M.H.); Institute for Biomedicine, Anhui Medical University, Hefei,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoshu","family":"Cheng","sequence":"additional","affiliation":[{"name":"From the National Clinical Research Study Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (M.Z., X.Q., B.W., F.F.H.); Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD (X.W.); Department of Neurology, First People\u2019s Hospital, Lianyungang, China (M.H.); Institute for Biomedicine, Anhui Medical University, Hefei,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binyan","family":"Wang","sequence":"additional","affiliation":[{"name":"From the National Clinical Research Study Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (M.Z., X.Q., B.W., F.F.H.); Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD (X.W.); Department of Neurology, First People\u2019s Hospital, Lianyungang, China (M.H.); Institute for Biomedicine, Anhui Medical University, Hefei,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan Fan","family":"Hou","sequence":"additional","affiliation":[{"name":"From the National Clinical Research Study Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (M.Z., X.Q., B.W., F.F.H.); Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD (X.W.); Department of Neurology, First People\u2019s Hospital, Lianyungang, China (M.H.); Institute for Biomedicine, Anhui Medical University, Hefei,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningling","family":"Sun","sequence":"additional","affiliation":[{"name":"From the National Clinical Research Study Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (M.Z., X.Q., B.W., F.F.H.); Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD (X.W.); Department of Neurology, First People\u2019s Hospital, Lianyungang, China (M.H.); Institute for Biomedicine, Anhui Medical University, Hefei,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yefeng","family":"Cai","sequence":"additional","affiliation":[{"name":"From the National Clinical Research Study Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (M.Z., X.Q., B.W., F.F.H.); Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD (X.W.); Department of Neurology, First People\u2019s Hospital, Lianyungang, China (M.H.); Institute for Biomedicine, Anhui Medical University, Hefei,..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)61097-1"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61728-0"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.111.635755"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.numecd.2014.05.011"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2014.04.011"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.3109\/10641963.2015.1026039"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60872-6"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/1476-511X-5-1"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.107.513416"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2011.02.010"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001177"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2013.09.066"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00394-014-0659-2"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.316.7135.894"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.2274"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2016.4687"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.116.014578"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1515\/jtim-2015-0027"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.1961"},{"key":"e_1_3_3_21_2","first-page":"233","article-title":"Evaluation of homocysteine level as a risk factor among patients with ischemic stroke and its subtypes.","volume":"38","author":"Ashjazadeh N","year":"2013","unstructured":"Ashjazadeh N, Fathi M, Shariat A. 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