{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:19:14Z","timestamp":1787015954190,"version":"build-2736575974"},"reference-count":34,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2014,10,8]],"date-time":"2014-10-08T00:00:00Z","timestamp":1412726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Oral Diseases"],"published-print":{"date-parts":[[2015,4]]},"abstract":"\n Objectives<\/jats:title>\n \n We investigated the relationship between non\u2010syndromic cleft lip\/palate (\n NSCLP<\/jats:styled-content>\n ) and polymorphisms in methylenetetrahydrofolate reductase (\n MTHFR<\/jats:styled-content>\n ), methionine synthase (\n MTR<\/jats:styled-content>\n ), methionine synthase reductase (\n MTRR<\/jats:styled-content>\n ), and\n RFC<\/jats:styled-content>\n 1, as well as the corresponding interactions with environmental factors.\n <\/jats:p>\n <\/jats:sec>\n \n Subjects and Methods<\/jats:title>\n \n One hundred and forty\n NSCLP<\/jats:styled-content>\n patients and their mothers, as well as 175 control individuals and their mothers, were recruited. Information regarding smoking and alcohol consumption was recorded. Blood samples were obtained in order to measure serum folate and cobalamin, as well as, plasma total homocysteine concentrations and to extract DNA. Polymorphisms in\n MTHFR<\/jats:styled-content>\n (677C>T and 1298A>C),\n MTR<\/jats:styled-content>\n (2756A>G),\n MTR<\/jats:styled-content>\n (66A>G), and\n RFC<\/jats:styled-content>\n 1(80A>G) were analyzed by\n PCR<\/jats:styled-content>\n \u2013restriction fragment length polymorphism.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Among the patients, 59.5% had cleft lip and palate, 22.0% had cleft palate, and 18.5% had cleft lip only. Maternal alcohol consumption and reduced folic acid concentrations in both children and mothers (\n P<\/jats:italic>\n \u00a0<\u00a00.001 and\n P<\/jats:italic>\n \u00a0=\u00a00.003, respectively) were risk factors for\n NSCLP<\/jats:styled-content>\n . Patients and their mothers carrying the\n MTHFR<\/jats:styled-content>\n 667T allele showed lower serum folate than\n CC<\/jats:styled-content>\n (\n P<\/jats:italic>\n \u00a0=\u00a00.011 and\n P<\/jats:italic>\n \u00a0=\u00a00.030, respectively). Mothers who carried the\n MTHFR<\/jats:styled-content>\n 1298C allele exhibited increased risk of having a child with\n NSCLP<\/jats:styled-content>\n , after adjusting for alcohol consumption (\n OR<\/jats:styled-content>\n : 1.75, 95%\n CI<\/jats:styled-content>\n : 1.03\u20132.99,\n P<\/jats:italic>\n \u00a0=\u00a00.038).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Reduced folic acid levels, alcohol consumption, and the\n MTHFR<\/jats:styled-content>\n 677T and 1298C alleles may have contributed to\n NSCLP<\/jats:styled-content>\n development in this sample population from Rio Grande do Norte.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/odi.12292","type":"journal-article","created":{"date-parts":[[2014,9,14]],"date-time":"2014-09-14T23:55:21Z","timestamp":1410738921000},"page":"393-399","source":"Crossref","is-referenced-by-count":55,"title":["Genetic and non\u2010genetic factors that increase the risk of non\u2010syndromic cleft lip and\/or palate development"],"prefix":"10.1111","volume":"21","author":[{"given":"JF","family":"Bezerra","sequence":"first","affiliation":[{"name":"Department of Clinical and Toxicological Analysis Federal University of Rio Grande do Norte Natal RN Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"GHM","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analysis Federal University of Rio Grande do Norte Natal RN Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"CD","family":"Soares","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analysis Federal University of Rio Grande do Norte Natal RN Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ML","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analysis Federal University of Rio Grande do Norte Natal RN Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MAG","family":"Ururahy","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analysis Federal University of Rio Grande do Norte Natal RN Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"FPF","family":"Neto","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analysis Federal University of Rio Grande do Norte Natal RN Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LG","family":"Lima\u2010Neto","sequence":"additional","affiliation":[{"name":"Universidade CEUMA S\u00e3o Luis MA Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"AD","family":"Luchessi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analysis Federal University of Rio Grande do Norte Natal RN Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"VN","family":"Silbiger","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analysis Federal University of Rio Grande do Norte Natal RN Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"CM","family":"Fajardo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analysis School of Pharmaceutical Sciences University of S\u00e3o Paulo S\u00e3o Paulo SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SR","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Program for Children with Cleft lip and Palate Pediatric Hospital Professor Heriberto Ferreira Bezerra Federal University of Rio Grande do Norte Natal RN Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M das G","family":"Almeida","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analysis Federal University of Rio Grande do Norte Natal RN Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"RDC","family":"Hirata","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analysis School of Pharmaceutical Sciences University of S\u00e3o Paulo S\u00e3o Paulo SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"AA","family":"de Rezende","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analysis Federal University of Rio Grande do Norte Natal RN Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MH","family":"Hirata","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analysis School of Pharmaceutical Sciences University of S\u00e3o Paulo S\u00e3o Paulo SP 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