{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T10:42:06Z","timestamp":1772793726622,"version":"3.50.1"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,11,26]],"date-time":"2019-11-26T00:00:00Z","timestamp":1574726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100010751","name":"Fondo Nacional de Desarrollo Cient\u00edfico, Tecnol\u00f3gico y de Innovaci\u00f3n Tecnol\u00f3gica","doi-asserted-by":"publisher","award":["1170805"],"award-info":[{"award-number":["1170805"]}],"id":[{"id":"10.13039\/501100010751","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oral Diseases"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To assess the association between polymorphic variants from <jats:italic>SHMT1<\/jats:italic> and <jats:italic>MTHFS<\/jats:italic> genes, involved in the cytoplasmic futile folate cycle, and the risk of nonsyndromic cleft lip with or without cleft palate (NSCL\/P) in the Chilean population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Subjects and Methods<\/jats:title><jats:p>In a sample of 139 Chilean NSCL\/P cases and 278 controls, we obtained the genotypes for nine variants of <jats:italic>SHMT1<\/jats:italic> and <jats:italic>MTHFS<\/jats:italic> and the association between them and the phenotype was evaluated using odds ratios (OR) in additive (allele), dominant, and recessive models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After correction for multiple comparisons, only the variant rs1979277 (G\u00a0&gt;\u00a0A; p.Leu474Phe) from <jats:italic>SHMT1<\/jats:italic> showed a significant and protective effect for additive (OR 0.60; 95% CI 0.42\u20130.86; <jats:italic>p<\/jats:italic>\u00a0=\u00a0.0054, <jats:italic>q<\/jats:italic>\u00a0=\u00a00.0488) and dominant models (OR 0.48; 95% CI 0.29\u20130.75; <jats:italic>p<\/jats:italic>\u00a0=\u00a0.0009; <jats:italic>q<\/jats:italic>\u00a0=\u00a00.0081). Our bioinformatic prediction plus functional evidence from previous reports demonstrate that the A allele for this missense variant decreases the enzymatic activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Owing to the rs1979277 A allele, which reduces the cytoplasmic SHMT activity and\u00a0has a higher frequency in controls than in NSCL\/P cases, we hypothesized that a low enzyme activity may increase the cytoplasmic concentration of folates and, therefore, explain the protective role against OFCs.<\/jats:p><\/jats:sec>","DOI":"10.1111\/odi.13229","type":"journal-article","created":{"date-parts":[[2019,11,12]],"date-time":"2019-11-12T06:24:38Z","timestamp":1573539878000},"page":"159-165","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["A <i>SHMT1<\/i> variant decreases the risk of nonsyndromic cleft lip with or without cleft palate in Chile"],"prefix":"10.1111","volume":"26","author":[{"given":"Carlos","family":"Salamanca","sequence":"first","affiliation":[{"name":"Institute for Research in Dental Sciences School of Dentistry Universidad de Chile Santiago Chile"},{"name":"Research Centre in Dental Sciences (CICO) Dental School Universidad de La Frontera Temuco Chile"},{"name":"Universidad Adventista de Chile Chill\u00e1n Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricio","family":"Gonz\u00e1lez\u2010Hormaz\u00e1bal","sequence":"additional","affiliation":[{"name":"Human Genetics Program Institute of Biomedical Sciences School of Medicine Universidad de Chile Santiago Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea S.","family":"Recabarren","sequence":"additional","affiliation":[{"name":"Institute for Research in Dental Sciences School of Dentistry Universidad de Chile Santiago Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pamela A.","family":"Recabarren","sequence":"additional","affiliation":[{"name":"Institute for Research in Dental Sciences School of Dentistry Universidad de Chile Santiago Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Pantoja","sequence":"additional","affiliation":[{"name":"Unit of Oral and Maxillofacial Surgery Hospital Cl\u00ednico San Borja\u2010Arriaran Santiago de Chile Chile"},{"name":"Department of Oral and Maxillofacial Surgery School of Dentistry Universidad de Chile Santiago Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noemi","family":"Leiva","sequence":"additional","affiliation":[{"name":"Unit of Maxillofacial Malformations School of Dentistry Universidad de Chile Santiago Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosa","family":"Pardo","sequence":"additional","affiliation":[{"name":"Section of Genetics Hospital Cl\u00ednico Universidad de Chile Santiago Chile"},{"name":"Unit of 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