{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T17:06:38Z","timestamp":1764781598869},"reference-count":27,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2004,5,18]],"date-time":"2004-05-18T00:00:00Z","timestamp":1084838400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"FAEP"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2004,7,30]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hyperhomocysteinemia is a risk factor for thrombosis, and methylenetetrahydrofolate reductase (<jats:italic>MTHFR<\/jats:italic>) and methionine synthase reductase (<jats:italic>MTRR<\/jats:italic>) polymorphisms, folate, and B<jats:sub>12<\/jats:sub> levels could contribute to plasma homocysteine (Hcy) variation. Although well established in adults, few studies have been performed in childhood. In this study, we investigated association of polymorphisms C677T and A1298C in the <jats:italic>MTHFR<\/jats:italic> gene and A66G in the <jats:italic>MTRR<\/jats:italic> gene with Hcy levels in children. These polymorphisms, as well as Hcy, folate, and vitamin B<jats:sub>12<\/jats:sub> levels were investigated in 220 normal children with ages ranging from 1 to 8 years. Plasma Hcy, folate, and vitamin B<jats:sub>12<\/jats:sub> levels were normal in all children. None of the polymorphisms could be considered an independent risk factor for hyperhomocysteinemia during childhood. The median Hcy levels in 37 children (17%) doubly heterozygous for C677T and A1298C mutations in the <jats:italic>MTHFR<\/jats:italic> gene were not different from the other genotypes. However, the association of the different genotypes with Hcy, folate, and vitamin B<jats:sub>12<\/jats:sub> levels demonstrated significant <jats:italic>P<\/jats:italic>\u2010values. The folate levels demonstrated a statistically significant decrease (<jats:italic>P<\/jats:italic>\u2009=\u20090.0477) from the C677T mutation in the <jats:italic>MTHFR<\/jats:italic> gene (TT genotype) when compared to the other groups. Folate was the only independent risk factor for hyperhomocysteinemia. Thus, monitoring the concentrations of folate would be more helpful for evaluating hyperhomocysteinemia and for preventing cardiovascular disease. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.30108","type":"journal-article","created":{"date-parts":[[2004,5,18]],"date-time":"2004-05-18T23:01:03Z","timestamp":1084921263000},"page":"256-260","source":"Crossref","is-referenced-by-count":28,"title":["Polymorphisms in the methylenetetrahydrofolate reductase and methionine synthase reductase genes and homocysteine levels in Brazilian children"],"prefix":"10.1002","volume":"128A","author":[{"given":"Ana Claudia M.","family":"Al\u00e9ssio","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joyce M.","family":"Annichino\u2010Bizzacchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio P.","family":"Bydlowski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcos N.","family":"Eberlin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriana P.","family":"Vellasco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nelci Fenalti","family":"H\u00f6ehr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,5,18]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1055\/s-0038-1656059","article-title":"The mutation Ala677\u2192Val in the methylene tetrahydrofolate reductase gene: A risk factor for arterial disease and venous thrombosis","volume":"77","author":"Arruda VR","year":"1997","journal-title":"Thromb Haemost"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19980724)78:4<332::AID-AJMG5>3.0.CO;2-N"},{"key":"e_1_2_6_4_1","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1055\/s-0037-1614564","article-title":"The relationship of mutations in the MTHFR, prothrombin, and PAI\u20101 genes to plasma levels of homocysteine, prothrombin, and PAI\u20101 in children and adults","volume":"81","author":"Balasa VV","year":"1999","journal-title":"Thromb Haemost"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-4356(02)00434-1"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/3.9.2303"},{"key":"e_1_2_6_7_1","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1055\/s-0038-1657580","article-title":"Hyperhomocysteinemia as a risk factor for arterial and venous disease. A review of evidence and relevance","volume":"78","author":"Boers GH","year":"1997","journal-title":"Thromb Haemost"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1995.03530130055028"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/204748730000700306"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V90.1.1"},{"key":"e_1_2_6_11_1","first-page":"409","article-title":"Total plasma homocysteine levels. 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