{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T20:58:38Z","timestamp":1790974718902,"version":"4.1.0"},"reference-count":18,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2007,5,1]],"date-time":"2007-05-01T00:00:00Z","timestamp":1177977600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2007,5,1]],"date-time":"2007-05-01T00:00:00Z","timestamp":1177977600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2007,5,1]],"date-time":"2007-05-01T00:00:00Z","timestamp":1177977600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2007,5,1]],"date-time":"2007-05-01T00:00:00Z","timestamp":1177977600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2007,5,1]],"date-time":"2007-05-01T00:00:00Z","timestamp":1177977600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2007,5,1]],"date-time":"2007-05-01T00:00:00Z","timestamp":1177977600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2007,5,1]],"date-time":"2007-05-01T00:00:00Z","timestamp":1177977600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004243","name":"Prinses Beatrix Spierfonds","doi-asserted-by":"publisher","award":["C042083"],"award-info":[{"award-number":["C042083"]}],"id":[{"id":"10.13039\/501100004243","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002997","name":"Nierstichting","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002997","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Genetics and Metabolism"],"published-print":{"date-parts":[[2007,5]]},"DOI":"10.1016\/j.ymgme.2007.01.009","type":"journal-article","created":{"date-parts":[[2007,3,3]],"date-time":"2007-03-03T13:27:56Z","timestamp":1172928476000},"page":"98-103","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":37,"title":["Variation and expression of dihydrofolate reductase (DHFR) in relation to spina bifida"],"prefix":"10.1016","volume":"91","author":[{"given":"Ivon J.M.","family":"van der Linden","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uyen","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra G.","family":"Heil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Franke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Vloet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henkjan","family":"Gellekink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin den","family":"Heijer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henk J.","family":"Blom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ymgme.2007.01.009_bib1","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/S0140-6736(95)92778-6","article-title":"Risks of orofacial clefts in children born to women using multivitamins containing folic acid periconceptionally","volume":"346","author":"Shaw","year":"1995","journal-title":"Lancet"},{"key":"10.1016\/j.ymgme.2007.01.009_bib2","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1002\/bdra.20086","article-title":"Hungarian cohort-controlled trial of periconceptional multivitamin supplementation shows a reduction in certain congenital abnormalities","volume":"70","author":"Czeizel","year":"2004","journal-title":"Birth Defects Res. A Clin. Mol. Teratol."},{"key":"10.1016\/j.ymgme.2007.01.009_bib3","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1056\/NEJM199212243272602","article-title":"Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation","volume":"327","author":"Czeizel","year":"1992","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ymgme.2007.01.009_bib4","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/S0140-6736(80)90886-7","article-title":"Possible prevention of neural-tube defects by periconceptional vitamin supplementation","volume":"1","author":"Smithells","year":"1980","journal-title":"Lancet"},{"key":"10.1016\/j.ymgme.2007.01.009_bib5","doi-asserted-by":"crossref","unstructured":"Vitamin Study Research Group, Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group, Lancet 338 (1991) 131\u2013137.","DOI":"10.1016\/0140-6736(91)90133-A"},{"key":"10.1016\/j.ymgme.2007.01.009_bib6","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1038\/nrn1986","article-title":"Neural tube defects and folate: case far from closed","volume":"7","author":"Blom","year":"2006","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1016\/j.ymgme.2007.01.009_bib7","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/sj.ejhg.5201713","article-title":"Molecular genetic analysis of the human dihydrofolate reductase gene: relation with plasma total homocysteine, serum and red blood cell folate levels","volume":"15","author":"Gellekink","year":"2007","journal-title":"Eur. J. Hum. Genet."},{"key":"10.1016\/j.ymgme.2007.01.009_bib8","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1002\/ajmg.a.20505","article-title":"New 19 bp deletion polymorphism in intron-1 of dihydrofolate reductase (DHFR): a risk factor for spina bifida acting in mothers during pregnancy?","volume":"124A","author":"Johnson","year":"2004","journal-title":"Am. J. Med. Genet."},{"key":"10.1016\/j.ymgme.2007.01.009_bib9","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1007\/BF01900603","article-title":"Nine-bp repeat polymorphism in exon 1 of the hMSH3 gene","volume":"40","author":"Nakajima","year":"1995","journal-title":"Jpn. J. Hum. Genet."},{"key":"10.1016\/j.ymgme.2007.01.009_bib10","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1007\/s00109-006-0093-x","article-title":"The methionine synthase reductase 66A>G polymorphism is a maternal risk factor for spina bifida","volume":"84","author":"van der Linden","year":"2006","journal-title":"J. Mol. Med."},{"key":"10.1016\/j.ymgme.2007.01.009_bib11","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/S0140-6736(95)90008-X","article-title":"Is hyperhomocysteinaemia a risk factor for recurrent venous thrombosis?","volume":"345","author":"den Heijer","year":"1995","journal-title":"Lancet"},{"key":"10.1016\/j.ymgme.2007.01.009_bib12","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1161\/01.CIR.99.16.2070","article-title":"Hyperhomocysteinemia: a risk factor for ischemic stroke in children","volume":"99","author":"van Beynum","year":"1999","journal-title":"Circulation"},{"key":"10.1016\/j.ymgme.2007.01.009_bib13","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1177\/000456329503200218","article-title":"Three different methods for the determination of total homocysteine in plasma","volume":"32","author":"te Poele-Pothoff","year":"1995","journal-title":"Ann. Clin. Biochem."},{"key":"10.1016\/j.ymgme.2007.01.009_bib14","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/0003-2697(87)90021-2","article-title":"Single-step method of RNA isolation by acid guanidinium thiocyanate\u2013phenol\u2013chloroform extraction","volume":"162","author":"Chomczynski","year":"1987","journal-title":"Anal. Biochem."},{"key":"10.1016\/j.ymgme.2007.01.009_bib15","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(\u2212Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"10.1016\/j.ymgme.2007.01.009_bib16","doi-asserted-by":"crossref","DOI":"10.1186\/gb-2002-3-7-research0034","article-title":"Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes","volume":"3","author":"Vandesompele","year":"2002","journal-title":"Genome Biol."},{"key":"10.1016\/j.ymgme.2007.01.009_bib17","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1093\/bioinformatics\/19.1.149","article-title":"Genetic Power Calculator: design of linkage and association genetic mapping studies of complex traits","volume":"19","author":"Purcell","year":"2003","journal-title":"Bioinformatics"},{"key":"10.1016\/j.ymgme.2007.01.009_bib18","doi-asserted-by":"crossref","first-page":"38292","DOI":"10.1074\/jbc.M212746200","article-title":"An intron is required for dihydrofolate reductase protein stability","volume":"278","author":"Noe","year":"2003","journal-title":"J. Biol. Chem."}],"container-title":["Molecular Genetics and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1096719207000339?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1096719207000339?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T23:17:41Z","timestamp":1761088661000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1096719207000339"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,5]]},"references-count":18,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2007,5]]}},"alternative-id":["S1096719207000339"],"URL":"https:\/\/doi.org\/10.1016\/j.ymgme.2007.01.009","relation":{},"ISSN":["1096-7192"],"issn-type":[{"value":"1096-7192","type":"print"}],"subject":[],"published":{"date-parts":[[2007,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Variation and expression of dihydrofolate reductase (DHFR) in relation to spina bifida","name":"articletitle","label":"Article Title"},{"value":"Molecular Genetics and Metabolism","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ymgme.2007.01.009","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2007 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}