{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:53:02Z","timestamp":1787017982413,"version":"build-2736575974"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2000,8]]},"abstract":"<jats:p>\n                    <jats:italic>Abstract<\/jats:italic>\n                    \u2014Although the major biochemical abnormality due to methylenetetrahydrofolate reductase (MTHFR) deficiency is hyperhomocyst(e)inemia, its pathogenicity appears to involve more than homocysteine toxicity. In patients with severe MTHFR deficiency, a metabolite(s) other than hyperhomocyst(e)inemia also appears to be associated with its clinical manifestation in cerebrovascular disease. To elucidate the specific role of the TT genotype of MTHFR in the development of cerebral infarction with and without cognitive impairment, we determined the prevalence of hyperhomocyst(e)inemia and the C677T genotypes of MTHFR in 143 patients with vascular dementia, 122 patients with cerebral infarction, and 217 healthy subjects matched for age and sex. Prevalence of hyperhomocyst(e)inemia [homocyst(e)ine \u226515 \u03bcmol\/L] was higher in cerebrovascular patients with or without dementia than in normal control subjects (42.6%, 20.5%, and 10.1%, respectively;\n                    <jats:italic>P<\/jats:italic>\n                    =0.001). In contrast, a higher frequency of MTHFR TT genotype was found only in demented patients compared with nondemented patients and healthy controls (25.2%, 9.8%, and 12.0%, respectively;\n                    <jats:italic>P<\/jats:italic>\n                    =0.01). When the study subjects were divided into normohomocyst(e)inemic and hyperhomocyst(e)inemic groups, the TT genotype was significantly associated with the risk for vascular dementia in the hyperhomocyst(e)inemic group (odds ratio 4.13, 95% CI 2.18 to 7.85;\n                    <jats:italic>P<\/jats:italic>\n                    =0.03) but not in the normohomocyst(e)inemic group. Demented patients with multiple infarcts had a higher frequency of TT genotype (odds ratio 3.13, 95% CI 2.23 to 4.39;\n                    <jats:italic>P<\/jats:italic>\n                    =0.0007), whereas those with a single infarct did not (odds ratio 2.03,\n                    <jats:italic>P<\/jats:italic>\n                    =0.15). In contrast, there was no significant association of the TT genotype with multiple infarcts in hyperhomocyst(e)inemic stroke patients. Taken together, these findings indicate a possible role of MTHFR TT genotype combined with hyperhomocyst(e)inemia in the pathogenesis of vascular dementia. Similar to the relationship between homocystinuria due to severe MTHFR deficiency and severe cystathionine \u03b2-synthase deficiency, the TT genotype of MTHFR in hyperhomocyst(e)inemic subjects is differentiated from the cases of the TT genotype without hyperhomocyst(e)inemia or hyperhomocyst(e)inemia without the TT genotype in the development of cerebrovascular disease.\n                  <\/jats:p>","DOI":"10.1161\/01.atv.20.8.1921","type":"journal-article","created":{"date-parts":[[2011,6,17]],"date-time":"2011-06-17T15:44:19Z","timestamp":1308325459000},"page":"1921-1925","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":41,"title":["Pathogenicity of Thermolabile Methylenetetrahydrofolate Reductase for Vascular Dementia"],"prefix":"10.1161","volume":"20","author":[{"given":"Jun-Hyun","family":"Yoo","sequence":"first","affiliation":[{"name":"From the Department of Family Medicine (J.-H.Y.), Samsung Medical Center, Center for Clinical Research, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, South Korea; the Department of Geriatric Medicine (G.-D.C.), Inchon Eun-Hye Hospital, Neuropsychiatric Hospital, Inchon, South Korea; and the Section of Genetics (S.-S.K.), Department of Pediatrics, Rush Medical College and Rush-Presbyterian-St. Luke\u2019s Medical Center, Chicago, Ill."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyu-Dong","family":"Choi","sequence":"additional","affiliation":[{"name":"From the Department of Family Medicine (J.-H.Y.), Samsung Medical Center, Center for Clinical Research, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, South Korea; the Department of Geriatric Medicine (G.-D.C.), Inchon Eun-Hye Hospital, Neuropsychiatric Hospital, Inchon, South Korea; and the Section of Genetics (S.-S.K.), Department of Pediatrics, Rush Medical College and Rush-Presbyterian-St. Luke\u2019s Medical Center, Chicago, Ill."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo-Sang","family":"Kang","sequence":"additional","affiliation":[{"name":"From the Department of Family Medicine (J.-H.Y.), Samsung Medical Center, Center for Clinical Research, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, South Korea; the Department of Geriatric Medicine (G.-D.C.), Inchon Eun-Hye Hospital, Neuropsychiatric Hospital, Inchon, South Korea; and the Section of Genetics (S.-S.K.), Department of Pediatrics, Rush Medical College and Rush-Presbyterian-St. Luke\u2019s Medical Center, Chicago, Ill."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","first-page":"473","volume":"114","year":"1989","journal-title":"J Lab Clin Med"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nu.12.070192.001431"},{"key":"e_1_3_2_3_2","first-page":"414","volume":"43","year":"1988","journal-title":"Am J Hum Genet"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0595-111"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.28.9.1739"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvb.18.9.1465"},{"key":"e_1_3_2_7_2","first-page":"208","volume":"99","year":"1999","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"e_1_3_2_8_2","unstructured":"Mudd SH Levy HL Skovby F. 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