{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T23:08:52Z","timestamp":1790291332307,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,1,22]],"date-time":"2009-01-22T00:00:00Z","timestamp":1232582400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2009,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND:<\/jats:title><jats:p>Spina bifida is a class of neural tube defects, which are congenital malformations of the central nervous system with a prevalence of 0.5 to 12 per 1000 births globally. In this article we attempt to identify genes related to folate and its metabolic pathways that are involved in the etiology of spina bifida.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS:<\/jats:title><jats:p>We selected 50 folate metabolism\u2013related genes and genotyped polymorphisms in those genes. Eighty\u2010seven polymorphisms in 45 genes passed quality controls. Associations with spina bifida were investigated in 180 patients and 190 controls. For those polymorphisms that were nominally associated with spina bifida risk, the relation with serum and red blood cell folate, vitamin B<jats:sub>12<\/jats:sub>, and homocysteine was evaluated in controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS:<\/jats:title><jats:p>A polymorphism in <jats:italic>CUBN<\/jats:italic> was significantly associated with decreased spina bifida risk, after correction for multiple testing, and was related to increased vitamin B<jats:sub>12<\/jats:sub> (<jats:italic>p<\/jats:italic> = 0.039) and red blood cell folate (<jats:italic>p<\/jats:italic> = 0.001). The <jats:italic>CUBN<\/jats:italic> gene encodes the intrinsic factor\u2013cobalamin receptor (or cubilin), a peripheral membrane protein that acts as a receptor for intrinsic factor\u2013vitamin B<jats:sub>12<\/jats:sub> complexes. Vitamin B<jats:sub>12<\/jats:sub> is an important cofactor in the folate metabolism, and low B<jats:sub>12<\/jats:sub> status in mothers has been linked to neural tube defects in children. Other interesting findings include nominally significant associations with polymorphisms in <jats:italic>TRDMT1<\/jats:italic>, <jats:italic>ALDH1L1<\/jats:italic>, <jats:italic>SARDH<\/jats:italic>, and <jats:italic>SLCA19A1 (RFC1<\/jats:italic>).<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION:<\/jats:title><jats:p>Our study indicates interesting new candidate genes and functional pathways for further study and confirms earlier findings. None of the genes <jats:italic>CUBN<\/jats:italic>, <jats:italic>TRDMT1<\/jats:italic>, <jats:italic>ALDH1L1<\/jats:italic>, or <jats:italic>SARDH<\/jats:italic> have been investigated previously for association with spina bifida. Birth Defects Research (Part A) 2009. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdra.20556","type":"journal-article","created":{"date-parts":[[2009,1,22]],"date-time":"2009-01-22T20:55:02Z","timestamp":1232657702000},"page":"216-226","source":"Crossref","is-referenced-by-count":69,"title":["An association study of 45 folate\u2010related genes in spina bifida: Involvement of <i>cubilin<\/i> (<i>CUBN<\/i>) and <i>tRNA aspartic acid methyltransferase 1<\/i> (<i>TRDMT1<\/i>)"],"prefix":"10.1002","volume":"85","author":[{"given":"Barbara","family":"Franke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sita H.H.M.","family":"Vermeulen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regine P.M.","family":"Steegers\u2010Theunissen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marieke J.","family":"Coenen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mascha M.V.A.P.","family":"Schijvenaars","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Scheffer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"den Heijer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henk 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