{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T20:29:52Z","timestamp":1776371392643,"version":"3.51.2"},"reference-count":58,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,3,24]],"date-time":"2015-03-24T00:00:00Z","timestamp":1427155200000},"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":[[2015,4]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The <jats:italic>MTHFR<\/jats:italic> rs1801131A&gt;C and rs1801133C&gt;T variants have been analyzed as putative genetic risk factors for oral clefts within various populations worldwide.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To test the role of these polymorphisms in nonsyndromic cleft lip with or without cleft palate (NSCL\/P) in the Brazilian population, we conducted a study combining a Family\u2010Based Association Test (transmission disequilibrium test) and a structured association analysis (case\u2013control study) based on the individual ancestry proportions. The rs1801131 and rs1801133 were initially analyzed in 197 case\u2010parent trios by transmission disequilibrium test, and polymorphisms showing significant association with NSCL\/P were subsequently studied in independent sample composed of 318 isolated samples of NSCL\/P and 598 healthy controls in a case\u2013control approach. Genomic ancestry was characterized by a set of 40 biallelic short insertion\/deletion markers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A strong overtransmission of the T allele of rs1801133 was observed in case\u2010parent trios of NSCL\/P (<jats:italic>p<\/jats:italic>\u2009=\u20090.002), but no preferential parent\u2010of\u2010origin transmission was detected. No association of rs1801131 polymorphism with NSCL\/P was observed. The structured case\u2013control analysis supported that the T allele was significantly more frequent in the NSCL\/P group (odds ratio: 1.37; 95% CI: 1.12\u20131.69; <jats:italic>p<\/jats:italic>\u2009=\u20090.002) than in the control group. Both polymorphisms were in linkage disequilibrium (D\u2032\u2009=\u20090.94 and r<jats:sup>2<\/jats:sup>\u2009=\u20090.79), and haplotype\u2010transmission disequilibrium test for allelic combination of rs1801131 and rs1801133 showed a significant overtransmission of haplotype A\u2010T to the affected NSCL\/P offspring (<jats:italic>p<\/jats:italic>\u2009=\u20090.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings provide evidences for the involvement of rs1801133 in the development of NSCL\/P in the Brazilian population. Birth Defects Research (Part A) 103:292\u2013298, 2015. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdra.23365","type":"journal-article","created":{"date-parts":[[2015,3,24]],"date-time":"2015-03-24T21:55:24Z","timestamp":1427234124000},"page":"292-298","source":"Crossref","is-referenced-by-count":19,"title":["rs1801133C&gt;T polymorphism in <i>MTHFR<\/i> is a risk factor for nonsyndromic cleft lip with or without cleft palate in the Brazilian population"],"prefix":"10.1002","volume":"103","author":[{"given":"Pamella Kelly Farias","family":"de Aguiar","sequence":"first","affiliation":[{"name":"Graduate Program in Molecular and Celular Biology \u2010 Federal University of Para\u00edba Jo\u00e3o Pessoa Para\u00edba Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo D.","family":"Coletta","sequence":"additional","affiliation":[{"name":"Department of Oral Diagnosis School of Dentistry State University of Campinas Piracicaba 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Oliveira","sequence":"additional","affiliation":[{"name":"Hospital Lauro Wanderley Hospital \u2010 Federal University of Para\u00edba Jo\u00e3o Pessoa Para\u00edba Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sibele Nascimento","family":"de Aquino","sequence":"additional","affiliation":[{"name":"Stomatology Clinic Dental School State University of Montes Claros Montes Claros Minas Gerais Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hercilio","family":"Martelli\u2010Junior","sequence":"additional","affiliation":[{"name":"Stomatology Clinic Dental School State University of Montes Claros Montes Claros Minas Gerais Brazil"},{"name":"Center for Rehabilitation of Craniofacial Anomalies Dental School University of Jos\u00e9 Rosario Vellano Alfenas Minas Gerais Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia Regina","family":"de Almeida Reis","sequence":"additional","affiliation":[{"name":"Department of Basic 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