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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Folic Acid Supplementation Use and the <italic>MTHFR</italic>
C677T Polymorphism in Orofacial Clefts Etiology: An Individual Participant Data Pooled-Analysis</title>
<author><name sortKey="Butali, Azeez" sort="Butali, Azeez" uniqKey="Butali A" first="Azeez" last="Butali">Azeez Butali</name>
<affiliation><nlm:aff id="A1">Department of Pediatrics, University of Iowa, U.S.A</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Little, Julian" sort="Little, Julian" uniqKey="Little J" first="Julian" last="Little">Julian Little</name>
<affiliation><nlm:aff id="A2">Department of Epidemiology and Community Medicine, University of Ottawa, Canada</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chevrier, Cecile" sort="Chevrier, Cecile" uniqKey="Chevrier C" first="Cécile" last="Chevrier">Cécile Chevrier</name>
<affiliation><nlm:aff id="A3">Institut National de la Santé et de Recherche Médicale, Rennes, France</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Cordier, Sylvian" sort="Cordier, Sylvian" uniqKey="Cordier S" first="Sylvian" last="Cordier">Sylvian Cordier</name>
<affiliation><nlm:aff id="A3">Institut National de la Santé et de Recherche Médicale, Rennes, France</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Steegers Theunissen, Regine" sort="Steegers Theunissen, Regine" uniqKey="Steegers Theunissen R" first="Regine" last="Steegers-Theunissen">Regine Steegers-Theunissen</name>
<affiliation><nlm:aff id="A4">Department of Obstetrics and Gynecology, Erasmus Medical Center, 3000 DR Rotterdam, The Netherlands</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A5">Department of Epidemiology, Radboud University Medical Center, Nijmegen, The Netherlands</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Jugessur, Astanand" sort="Jugessur, Astanand" uniqKey="Jugessur A" first="Astanand" last="Jugessur">Astanand Jugessur</name>
<affiliation><nlm:aff id="A6">Division of Epidemiology, Norwegian Institute of Public Health, N-0403 Oslo, Norway</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A7">Craniofacial Research, Murdoch Childrens Research Institute, Royal Children's Hospital, 3052 Parkville, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Oladugba, Bola" sort="Oladugba, Bola" uniqKey="Oladugba B" first="Bola" last="Oladugba">Bola Oladugba</name>
<affiliation><nlm:aff id="A8">Department of Statistics, University of Nigeria, Nsukka, Nigeria</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mossey, Peter A" sort="Mossey, Peter A" uniqKey="Mossey P" first="Peter A." last="Mossey">Peter A. Mossey</name>
<affiliation><nlm:aff id="A9">Dundee Dental School and Hospital, University of Dundee, UK</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">23670871</idno>
<idno type="pmc">3745533</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3745533</idno>
<idno type="RBID">PMC:3745533</idno>
<idno type="doi">10.1002/bdra.23133</idno>
<date when="2013">2013</date>
<idno type="wicri:Area/Pmc/Corpus">001E15</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001E15</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Folic Acid Supplementation Use and the <italic>MTHFR</italic>
C677T Polymorphism in Orofacial Clefts Etiology: An Individual Participant Data Pooled-Analysis</title>
<author><name sortKey="Butali, Azeez" sort="Butali, Azeez" uniqKey="Butali A" first="Azeez" last="Butali">Azeez Butali</name>
<affiliation><nlm:aff id="A1">Department of Pediatrics, University of Iowa, U.S.A</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Little, Julian" sort="Little, Julian" uniqKey="Little J" first="Julian" last="Little">Julian Little</name>
<affiliation><nlm:aff id="A2">Department of Epidemiology and Community Medicine, University of Ottawa, Canada</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chevrier, Cecile" sort="Chevrier, Cecile" uniqKey="Chevrier C" first="Cécile" last="Chevrier">Cécile Chevrier</name>
<affiliation><nlm:aff id="A3">Institut National de la Santé et de Recherche Médicale, Rennes, France</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Cordier, Sylvian" sort="Cordier, Sylvian" uniqKey="Cordier S" first="Sylvian" last="Cordier">Sylvian Cordier</name>
<affiliation><nlm:aff id="A3">Institut National de la Santé et de Recherche Médicale, Rennes, France</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Steegers Theunissen, Regine" sort="Steegers Theunissen, Regine" uniqKey="Steegers Theunissen R" first="Regine" last="Steegers-Theunissen">Regine Steegers-Theunissen</name>
<affiliation><nlm:aff id="A4">Department of Obstetrics and Gynecology, Erasmus Medical Center, 3000 DR Rotterdam, The Netherlands</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A5">Department of Epidemiology, Radboud University Medical Center, Nijmegen, The Netherlands</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Jugessur, Astanand" sort="Jugessur, Astanand" uniqKey="Jugessur A" first="Astanand" last="Jugessur">Astanand Jugessur</name>
<affiliation><nlm:aff id="A6">Division of Epidemiology, Norwegian Institute of Public Health, N-0403 Oslo, Norway</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A7">Craniofacial Research, Murdoch Childrens Research Institute, Royal Children's Hospital, 3052 Parkville, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Oladugba, Bola" sort="Oladugba, Bola" uniqKey="Oladugba B" first="Bola" last="Oladugba">Bola Oladugba</name>
<affiliation><nlm:aff id="A8">Department of Statistics, University of Nigeria, Nsukka, Nigeria</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mossey, Peter A" sort="Mossey, Peter A" uniqKey="Mossey P" first="Peter A." last="Mossey">Peter A. Mossey</name>
<affiliation><nlm:aff id="A9">Dundee Dental School and Hospital, University of Dundee, UK</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Birth defects research. Part A, Clinical and molecular teratology</title>
<idno type="ISSN">1542-0752</idno>
<idno type="eISSN">1542-0760</idno>
<imprint><date when="2013">2013</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><sec id="S1"><title>Background</title>
<p id="P1">This study examines gene-environment interaction (GEI) between the <italic>MTHFR</italic>
C667T polymorphism and folic acid in the etiology of orofacial clefts (OFC). We used a pooled-analyticapproach on four studies that used similar methods.</p>
</sec>
<sec id="S2"><title>Methods</title>
<p id="P2">We used logistic regression to analyse the pooled sample of 1149 isolated cases and 1161 controls. Fetal and maternal <italic>MTHFR</italic>
C677T genotypes, and maternal periconceptional exposure to smoking, alcohol, vitamin containing folic acid and folic acid supplements were contrasted between the cleft types [non-syndromic clefts lip or without cleft palate (CL(P)) and non syndromic cleft palate (CP)] and control groups.</p>
</sec>
<sec id="S3"><title>Results</title>
<p id="P3">There was a reduced risk of CL(P) with maternal folic acid use (<italic>p</italic>
=0.008; OR=0.70, 95% CI: 0.65–0.94) and with supplements containing folic acid (<italic>p</italic>
=0.028, OR=0.80, 95% CI: 0.65–0.94). Maternal smoking increased the risk of both CL(P) (<italic>p</italic>
<10e−3; OR=1.62, 95% CI: 1.35–1.95) and CP (<italic>p</italic>
=0.028; OR=1.38, 95% CI: 1.04–1.83). No significant risk was observed with either maternal or fetal <italic>MTHFR</italic>
C677T genotypes.</p>
</sec>
<sec id="S4"><title>Conclusion</title>
<p id="P4">This individual paticipant data (IPD) meta-analysis affords greater statistical power and can help alleviate the problems associated with aggregate-level data-sharing. The result of this IPD meta-analysis is consistent with previous reports suggesting that folic acid and smoking influence OFC outcomes.</p>
</sec>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">101155107</journal-id>
<journal-id journal-id-type="pubmed-jr-id">30290</journal-id>
<journal-id journal-id-type="nlm-ta">Birth Defects Res A Clin Mol Teratol</journal-id>
<journal-id journal-id-type="iso-abbrev">Birth Defects Res. Part A Clin. Mol. Teratol.</journal-id>
<journal-title-group><journal-title>Birth defects research. Part A, Clinical and molecular teratology</journal-title>
</journal-title-group>
<issn pub-type="ppub">1542-0752</issn>
<issn pub-type="epub">1542-0760</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">23670871</article-id>
<article-id pub-id-type="pmc">3745533</article-id>
<article-id pub-id-type="doi">10.1002/bdra.23133</article-id>
<article-id pub-id-type="manuscript">NIHMS464334</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Folic Acid Supplementation Use and the <italic>MTHFR</italic>
C677T Polymorphism in Orofacial Clefts Etiology: An Individual Participant Data Pooled-Analysis</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Butali</surname>
<given-names>Azeez</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Little</surname>
<given-names>Julian</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chevrier</surname>
<given-names>Cécile</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Cordier</surname>
<given-names>Sylvian</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Steegers-Theunissen</surname>
<given-names>Regine</given-names>
</name>
<xref ref-type="aff" rid="A4">4</xref>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jugessur</surname>
<given-names>Astanand</given-names>
</name>
<xref ref-type="aff" rid="A6">6</xref>
<xref ref-type="aff" rid="A7">7</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Oladugba</surname>
<given-names>Bola</given-names>
</name>
<xref ref-type="aff" rid="A8">8</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Mossey</surname>
<given-names>Peter A.</given-names>
</name>
<xref ref-type="aff" rid="A9">9</xref>
</contrib>
</contrib-group>
<aff id="A1"><label>1</label>
Department of Pediatrics, University of Iowa, U.S.A</aff>
<aff id="A2"><label>2</label>
Department of Epidemiology and Community Medicine, University of Ottawa, Canada</aff>
<aff id="A3"><label>3</label>
Institut National de la Santé et de Recherche Médicale, Rennes, France</aff>
<aff id="A4"><label>4</label>
Department of Obstetrics and Gynecology, Erasmus Medical Center, 3000 DR Rotterdam, The Netherlands</aff>
<aff id="A5"><label>5</label>
Department of Epidemiology, Radboud University Medical Center, Nijmegen, The Netherlands</aff>
<aff id="A6"><label>6</label>
Division of Epidemiology, Norwegian Institute of Public Health, N-0403 Oslo, Norway</aff>
<aff id="A7"><label>7</label>
Craniofacial Research, Murdoch Childrens Research Institute, Royal Children's Hospital, 3052 Parkville, Australia</aff>
<aff id="A8"><label>8</label>
Department of Statistics, University of Nigeria, Nsukka, Nigeria</aff>
<aff id="A9"><label>9</label>
Dundee Dental School and Hospital, University of Dundee, UK</aff>
<author-notes><corresp id="cor1">Corresponding Author: Azeez Butali, Department of Pediatrics, University of Iowa, 500 Newton Road, Iowa City, Iowa. 52242, <email>Azeez-butali@uiowa.edu</email>
</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>22</day>
<month>4</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="epub"><day>13</day>
<month>5</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="ppub"><month>8</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>01</day>
<month>8</month>
<year>2014</year>
</pub-date>
<volume>97</volume>
<issue>8</issue>
<elocation-id>10.1002/bdra.23133</elocation-id>
<abstract><sec id="S1"><title>Background</title>
<p id="P1">This study examines gene-environment interaction (GEI) between the <italic>MTHFR</italic>
C667T polymorphism and folic acid in the etiology of orofacial clefts (OFC). We used a pooled-analyticapproach on four studies that used similar methods.</p>
</sec>
<sec id="S2"><title>Methods</title>
<p id="P2">We used logistic regression to analyse the pooled sample of 1149 isolated cases and 1161 controls. Fetal and maternal <italic>MTHFR</italic>
C677T genotypes, and maternal periconceptional exposure to smoking, alcohol, vitamin containing folic acid and folic acid supplements were contrasted between the cleft types [non-syndromic clefts lip or without cleft palate (CL(P)) and non syndromic cleft palate (CP)] and control groups.</p>
</sec>
<sec id="S3"><title>Results</title>
<p id="P3">There was a reduced risk of CL(P) with maternal folic acid use (<italic>p</italic>
=0.008; OR=0.70, 95% CI: 0.65–0.94) and with supplements containing folic acid (<italic>p</italic>
=0.028, OR=0.80, 95% CI: 0.65–0.94). Maternal smoking increased the risk of both CL(P) (<italic>p</italic>
<10e−3; OR=1.62, 95% CI: 1.35–1.95) and CP (<italic>p</italic>
=0.028; OR=1.38, 95% CI: 1.04–1.83). No significant risk was observed with either maternal or fetal <italic>MTHFR</italic>
C677T genotypes.</p>
</sec>
<sec id="S4"><title>Conclusion</title>
<p id="P4">This individual paticipant data (IPD) meta-analysis affords greater statistical power and can help alleviate the problems associated with aggregate-level data-sharing. The result of this IPD meta-analysis is consistent with previous reports suggesting that folic acid and smoking influence OFC outcomes.</p>
</sec>
</abstract>
<kwd-group><kwd>Cleft lip and palate</kwd>
<kwd><italic>MTHFR</italic>
</kwd>
<kwd>Folic acid</kwd>
<kwd>Individual patient data</kwd>
<kwd>pooled-analysis</kwd>
</kwd-group>
<funding-group><award-group><funding-source country="United States">National Institute of Dental and Craniofacial Research : NIDCR</funding-source>
<award-id>K99 DE022378 || DE</award-id>
</award-group>
</funding-group>
</article-meta>
</front>
</pmc>
</record>
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