AustralieFrV1, Main, Exploration, bibRecord, 004824

Association between C677T Polymorphism of Methylene Tetrahydrofolate Reductase and Congenital Heart Disease: Meta-Analysis of 7,697 Cases and 13,125 Controls

Identifieur interne : 004824 ( Main/Exploration ); précédent : 004823; suivant : 004825

Association between C677T Polymorphism of Methylene Tetrahydrofolate Reductase and Congenital Heart Disease: Meta-Analysis of 7,697 Cases and 13,125 Controls

Auteurs : Chrysovalanto Mamasoula [Royaume-Uni] ; R. Reid Prentice ; Tomasz Pierscionek [Royaume-Uni] ; Faith Pangilinan ; James L. Mills [États-Unis] ; Charlotte Druschel ; Kenneth Pass [États-Unis] ; Mark W. Russell [États-Unis] ; Darroch Hall [Royaume-Uni] ; Ana Töpf [Royaume-Uni] ; Danielle L. Brown [Royaume-Uni] ; Diana Zelenika [France] ; Jamie Bentham [Royaume-Uni] ; Catherine Cosgrove [Royaume-Uni] ; Shoumo Bhattacharya [Royaume-Uni] ; Javier Granados Riveron ; Kerry Setchfield ; J. David Brook ; Frances A. Bu'Lock ; Chris Thornborough ; Thahira J. Rahman [Royaume-Uni] ; Julian Palomino Doza [Royaume-Uni] ; Huay L. Tan [Royaume-Uni] ; John O'Sullivan ; A. Graham Stuart [Royaume-Uni] ; Gillian Blue [Australie] ; David Winlaw [Australie] ; Alex V. Postma [Pays-Bas] ; Barbara J. M. Mulder [Pays-Bas] ; Aelko H. Zwinderman [Pays-Bas] ; Klaartje Van Engelen [Pays-Bas] ; Antoon F. M. Moorman [Pays-Bas] ; Anita Rauch [Suisse] ; Marc Gewillig [Belgique] ; Jeroen Breckpot [Belgique] ; Koen Devriendt [Belgique] ; G. Mark Lathrop [France] ; Martin Farrall [Royaume-Uni] ; Judith A. Goodship [Royaume-Uni] ; Heather J. Cordell [Royaume-Uni] ; Lawrence C. Brody ; Bernard D. Keavney [Royaume-Uni]

Source :

Circulation. Cardiovascular genetics [ 1942-325X ] ; 2013.

RBID : PMC:3855044

Abstract

Background

Association between the C677T polymorphism of the methylene tetrahydrofolate reductase (MTHFR) gene and congenital heart disease (CHD) is contentious.

Methods and Results

We compared genotypes between CHD cases and controls, and between mothers of CHD cases and controls. We placed our results in context by conducting metaanalyses of previously published studies. Among 5,814 cases with primary genotype data and 10,056 controls, there was no evidence of association between MTHFR C677T genotype and CHD risk (OR 0.96 [95% CI 0.87-1.07]). A random-effects meta-analysis of all studies (involving 7,697 cases and 13,125 controls) suggested the presence of association (OR 1.25 [95% CI 1.03-1.51]; p=0.022), but with substantial heterogeneity among contributing studies (I²=64.4%), and evidence of publication bias. Meta-analysis of large studies only (defined by a variance of the log OR less than 0.05), which together contributed 83% of all cases, yielded no evidence of association (OR 0.97 [95% CI 0.91-1.03]), without significant heterogeneity (I²=0). Moreover, meta-analysis of 1,781 mothers of CHD cases (829 of whom were genotyped in this study) and 19,861 controls revealed no evidence of association between maternal C677T genotype and risk of CHD in offspring (OR 1.13 [95% CI 0.87-1.47]). There was no significant association between MTHFR genotype and CHD risk in large studies from regions with different levels of dietary folate.

Conclusions

The MTHFR C677T polymorphism, which directly influences plasma folate levels, is not associated with CHD risk. Publication biases appear to substantially contaminate the literature with regard to this genetic association.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3855044

DOI: 10.1161/CIRCGENETICS.113.000191
PubMed: 23876493
PubMed Central: 3855044

Affiliations:

Le document en format XML

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<author><name sortKey="Cosgrove, Catherine" sort="Cosgrove, Catherine" uniqKey="Cosgrove C" first="Catherine" last="Cosgrove">Catherine Cosgrove</name>
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<author><name sortKey="Bhattacharya, Shoumo" sort="Bhattacharya, Shoumo" uniqKey="Bhattacharya S" first="Shoumo" last="Bhattacharya">Shoumo Bhattacharya</name>
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<author><name sortKey="Riveron, Javier Granados" sort="Riveron, Javier Granados" uniqKey="Riveron J" first="Javier Granados" last="Riveron">Javier Granados Riveron</name>
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<author><name sortKey="Setchfield, Kerry" sort="Setchfield, Kerry" uniqKey="Setchfield K" first="Kerry" last="Setchfield">Kerry Setchfield</name>
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</author>
<author><name sortKey="Brook, J David" sort="Brook, J David" uniqKey="Brook J" first="J. David" last="Brook">J. David Brook</name>
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</affiliation>
</author>
<author><name sortKey="Bu Lock, Frances A" sort="Bu Lock, Frances A" uniqKey="Bu Lock F" first="Frances A." last="Bu'Lock">Frances A. Bu'Lock</name>
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<author><name sortKey="Thornborough, Chris" sort="Thornborough, Chris" uniqKey="Thornborough C" first="Chris" last="Thornborough">Chris Thornborough</name>
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</affiliation>
</author>
<author><name sortKey="Rahman, Thahira J" sort="Rahman, Thahira J" uniqKey="Rahman T" first="Thahira J." last="Rahman">Thahira J. Rahman</name>
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<author><name sortKey="Tan, Huay L" sort="Tan, Huay L" uniqKey="Tan H" first="Huay L." last="Tan">Huay L. Tan</name>
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<author><name sortKey="O Sullivan, John" sort="O Sullivan, John" uniqKey="O Sullivan J" first="John" last="O'Sullivan">John O'Sullivan</name>
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</affiliation>
</author>
<author><name sortKey="Stuart, A Graham" sort="Stuart, A Graham" uniqKey="Stuart A" first="A. Graham" last="Stuart">A. Graham Stuart</name>
<affiliation wicri:level="1"><nlm:aff id="A13">Bristol Royal Hospital for Children, Bristol, United Kingdom</nlm:aff>
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<wicri:regionArea>Bristol Royal Hospital for Children, Bristol</wicri:regionArea>
<wicri:noRegion>Bristol</wicri:noRegion>
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<author><name sortKey="Blue, Gillian" sort="Blue, Gillian" uniqKey="Blue G" first="Gillian" last="Blue">Gillian Blue</name>
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</author>
<author><name sortKey="Winlaw, David" sort="Winlaw, David" uniqKey="Winlaw D" first="David" last="Winlaw">David Winlaw</name>
<affiliation wicri:level="1"><nlm:aff id="A14">The Children's Hospital at Westmead, Westmead, Australia</nlm:aff>
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<wicri:regionArea>The Children's Hospital at Westmead, Westmead</wicri:regionArea>
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</author>
<author><name sortKey="Postma, Alex V" sort="Postma, Alex V" uniqKey="Postma A" first="Alex V." last="Postma">Alex V. Postma</name>
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<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Academic Medical Center, Amsterdam</wicri:regionArea>
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</placeName>
</affiliation>
</author>
<author><name sortKey="Mulder, Barbara J M" sort="Mulder, Barbara J M" uniqKey="Mulder B" first="Barbara J. M." last="Mulder">Barbara J. M. Mulder</name>
<affiliation wicri:level="3"><nlm:aff id="A15">Academic Medical Center, Amsterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Academic Medical Center, Amsterdam</wicri:regionArea>
<placeName><settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Zwinderman, Aelko H" sort="Zwinderman, Aelko H" uniqKey="Zwinderman A" first="Aelko H." last="Zwinderman">Aelko H. Zwinderman</name>
<affiliation wicri:level="3"><nlm:aff id="A15">Academic Medical Center, Amsterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Academic Medical Center, Amsterdam</wicri:regionArea>
<placeName><settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Van Engelen, Klaartje" sort="Van Engelen, Klaartje" uniqKey="Van Engelen K" first="Klaartje" last="Van Engelen">Klaartje Van Engelen</name>
<affiliation wicri:level="3"><nlm:aff id="A15">Academic Medical Center, Amsterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Academic Medical Center, Amsterdam</wicri:regionArea>
<placeName><settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Moorman, Antoon F M" sort="Moorman, Antoon F M" uniqKey="Moorman A" first="Antoon F. M." last="Moorman">Antoon F. M. Moorman</name>
<affiliation wicri:level="3"><nlm:aff id="A15">Academic Medical Center, Amsterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Academic Medical Center, Amsterdam</wicri:regionArea>
<placeName><settlement type="city">Amsterdam</settlement>
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</placeName>
</affiliation>
</author>
<author><name sortKey="Rauch, Anita" sort="Rauch, Anita" uniqKey="Rauch A" first="Anita" last="Rauch">Anita Rauch</name>
<affiliation wicri:level="4"><nlm:aff id="A16">Inst of Medical Genetics, University of Zurich, Switzerland</nlm:aff>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Inst of Medical Genetics, University of Zurich</wicri:regionArea>
<placeName><settlement type="city">Zurich</settlement>
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</placeName>
<orgName type="university">Université de Zurich</orgName>
</affiliation>
</author>
<author><name sortKey="Gewillig, Marc" sort="Gewillig, Marc" uniqKey="Gewillig M" first="Marc" last="Gewillig">Marc Gewillig</name>
<affiliation wicri:level="1"><nlm:aff id="A17">Pediatric Cardiology, University of Leuven, Leuven, Belgium</nlm:aff>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Pediatric Cardiology, University of Leuven, Leuven</wicri:regionArea>
<wicri:noRegion>Leuven</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Breckpot, Jeroen" sort="Breckpot, Jeroen" uniqKey="Breckpot J" first="Jeroen" last="Breckpot">Jeroen Breckpot</name>
<affiliation wicri:level="1"><nlm:aff id="A18">Center for Human Genetics, Univ of Leuven, Leuven, Belgium</nlm:aff>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Center for Human Genetics, Univ of Leuven, Leuven</wicri:regionArea>
<wicri:noRegion>Leuven</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Devriendt, Koen" sort="Devriendt, Koen" uniqKey="Devriendt K" first="Koen" last="Devriendt">Koen Devriendt</name>
<affiliation wicri:level="1"><nlm:aff id="A18">Center for Human Genetics, Univ of Leuven, Leuven, Belgium</nlm:aff>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Center for Human Genetics, Univ of Leuven, Leuven</wicri:regionArea>
<wicri:noRegion>Leuven</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Lathrop, G Mark" sort="Lathrop, G Mark" uniqKey="Lathrop G" first="G. Mark" last="Lathrop">G. Mark Lathrop</name>
<affiliation><nlm:aff id="A7">Commisariat àl'énergie Atomique (CEA), Institut Genomique, Centre National de Genotypage, Evry</nlm:aff>
<wicri:noCountry code="subfield">Evry</wicri:noCountry>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A8">Fondation Jean Dausset, Centre d'Etude du Polymorphism Human, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Fondation Jean Dausset, Centre d'Etude du Polymorphism Human, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Farrall, Martin" sort="Farrall, Martin" uniqKey="Farrall M" first="Martin" last="Farrall">Martin Farrall</name>
<affiliation wicri:level="3"><nlm:aff id="A9">Dept of Cardiovascular Medicine, Oxford University, Oxford</nlm:aff>
<country>Royaume-Uni</country>
<placeName><settlement type="city">Oxford</settlement>
<region type="country">Angleterre</region>
<region type="comté" nuts="2">Oxfordshire</region>
</placeName>
<wicri:orgArea>Dept of Cardiovascular Medicine, Oxford University</wicri:orgArea>
</affiliation>
</author>
<author><name sortKey="Goodship, Judith A" sort="Goodship, Judith A" uniqKey="Goodship J" first="Judith A." last="Goodship">Judith A. Goodship</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Inst of Genetic Medicine, Newcastle Univ, Newcastle upon Tyne, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Inst of Genetic Medicine, Newcastle Univ, Newcastle upon Tyne</wicri:regionArea>
<wicri:noRegion>Newcastle upon Tyne</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Cordell, Heather J" sort="Cordell, Heather J" uniqKey="Cordell H" first="Heather J." last="Cordell">Heather J. Cordell</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Inst of Genetic Medicine, Newcastle Univ, Newcastle upon Tyne, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Inst of Genetic Medicine, Newcastle Univ, Newcastle upon Tyne</wicri:regionArea>
<wicri:noRegion>Newcastle upon Tyne</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Brody, Lawrence C" sort="Brody, Lawrence C" uniqKey="Brody L" first="Lawrence C." last="Brody">Lawrence C. Brody</name>
<affiliation><nlm:aff id="A2">Molecular Pathogenesis Section, Genome Technology Branch, National Human Genome Research Inst</nlm:aff>
<wicri:noCountry code="subfield">National Human Genome Research Inst</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Keavney, Bernard D" sort="Keavney, Bernard D" uniqKey="Keavney B" first="Bernard D." last="Keavney">Bernard D. Keavney</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Inst of Genetic Medicine, Newcastle Univ, Newcastle upon Tyne, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Inst of Genetic Medicine, Newcastle Univ, Newcastle upon Tyne</wicri:regionArea>
<wicri:noRegion>Newcastle upon Tyne</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A19">Institute of Cardiovascular Sciences, The Univ of Manchester, Manchester, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Institute of Cardiovascular Sciences, The Univ of Manchester, Manchester</wicri:regionArea>
<placeName><settlement type="city">Manchester</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Manchester</region>
</placeName>
</affiliation>
</author>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Association between C677T Polymorphism of Methylene Tetrahydrofolate Reductase and Congenital Heart Disease: Meta-Analysis of 7,697 Cases and 13,125 Controls</title>
<author><name sortKey="Mamasoula, Chrysovalanto" sort="Mamasoula, Chrysovalanto" uniqKey="Mamasoula C" first="Chrysovalanto" last="Mamasoula">Chrysovalanto Mamasoula</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Inst of Genetic Medicine, Newcastle Univ, Newcastle upon Tyne, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Inst of Genetic Medicine, Newcastle Univ, Newcastle upon Tyne</wicri:regionArea>
<wicri:noRegion>Newcastle upon Tyne</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Prentice, R Reid" sort="Prentice, R Reid" uniqKey="Prentice R" first="R. Reid" last="Prentice">R. Reid Prentice</name>
<affiliation><nlm:aff id="A2">Molecular Pathogenesis Section, Genome Technology Branch, National Human Genome Research Inst</nlm:aff>
<wicri:noCountry code="subfield">National Human Genome Research Inst</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Pierscionek, Tomasz" sort="Pierscionek, Tomasz" uniqKey="Pierscionek T" first="Tomasz" last="Pierscionek">Tomasz Pierscionek</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Inst of Genetic Medicine, Newcastle Univ, Newcastle upon Tyne, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Inst of Genetic Medicine, Newcastle Univ, Newcastle upon Tyne</wicri:regionArea>
<wicri:noRegion>Newcastle upon Tyne</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Pangilinan, Faith" sort="Pangilinan, Faith" uniqKey="Pangilinan F" first="Faith" last="Pangilinan">Faith Pangilinan</name>
<affiliation><nlm:aff id="A2">Molecular Pathogenesis Section, Genome Technology Branch, National Human Genome Research Inst</nlm:aff>
<wicri:noCountry code="subfield">National Human Genome Research Inst</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Mills, James L" sort="Mills, James L" uniqKey="Mills J" first="James L." last="Mills">James L. Mills</name>
<affiliation wicri:level="2"><nlm:aff id="A3">Division of Epidemiology, Statistics & Prevention Research, Eunice Kennedy Shriver National Inst of Child Health & Human Development, National Institutes of Health, Dept of Health & Human Services, Bethesda, MD</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Division of Epidemiology, Statistics & Prevention Research, Eunice Kennedy Shriver National Inst of Child Health & Human Development, National Institutes of Health, Dept of Health & Human Services, Bethesda</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Druschel, Charlotte" sort="Druschel, Charlotte" uniqKey="Druschel C" first="Charlotte" last="Druschel">Charlotte Druschel</name>
<affiliation><nlm:aff id="A4">Congenital Malformations Registry, New York State Dept of Health, Troy & Dept of Epidemiology & Biostatistics, Univ at Albany School of Public Health, Rensselaer</nlm:aff>
<wicri:noCountry code="subfield">Rensselaer</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Pass, Kenneth" sort="Pass, Kenneth" uniqKey="Pass K" first="Kenneth" last="Pass">Kenneth Pass</name>
<affiliation wicri:level="2"><nlm:aff id="A5">Wadsworth Center, New York State Dept of Health, Albany, NY</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Wadsworth Center, New York State Dept of Health, Albany</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Russell, Mark W" sort="Russell, Mark W" uniqKey="Russell M" first="Mark W." last="Russell">Mark W. Russell</name>
<affiliation wicri:level="2"><nlm:aff id="A6">Dept of Pediatrics &Communicable Diseases, The Univ of Michigan Medical School, Ann Arbor, MI</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Michigan</region>
</placeName>
<wicri:cityArea>Dept of Pediatrics &Communicable Diseases, The Univ of Michigan Medical School, Ann Arbor</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Hall, Darroch" sort="Hall, Darroch" uniqKey="Hall D" first="Darroch" last="Hall">Darroch Hall</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Inst of Genetic Medicine, Newcastle Univ, Newcastle upon Tyne, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Inst of Genetic Medicine, Newcastle Univ, Newcastle upon Tyne</wicri:regionArea>
<wicri:noRegion>Newcastle upon Tyne</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Topf, Ana" sort="Topf, Ana" uniqKey="Topf A" first="Ana" last="Töpf">Ana Töpf</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Inst of Genetic Medicine, Newcastle Univ, Newcastle upon Tyne, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Inst of Genetic Medicine, Newcastle Univ, Newcastle upon Tyne</wicri:regionArea>
<wicri:noRegion>Newcastle upon Tyne</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Brown, Danielle L" sort="Brown, Danielle L" uniqKey="Brown D" first="Danielle L." last="Brown">Danielle L. Brown</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Inst of Genetic Medicine, Newcastle Univ, Newcastle upon Tyne, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Inst of Genetic Medicine, Newcastle Univ, Newcastle upon Tyne</wicri:regionArea>
<wicri:noRegion>Newcastle upon Tyne</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Zelenika, Diana" sort="Zelenika, Diana" uniqKey="Zelenika D" first="Diana" last="Zelenika">Diana Zelenika</name>
<affiliation><nlm:aff id="A7">Commisariat àl'énergie Atomique (CEA), Institut Genomique, Centre National de Genotypage, Evry</nlm:aff>
<wicri:noCountry code="subfield">Evry</wicri:noCountry>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A8">Fondation Jean Dausset, Centre d'Etude du Polymorphism Human, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Fondation Jean Dausset, Centre d'Etude du Polymorphism Human, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bentham, Jamie" sort="Bentham, Jamie" uniqKey="Bentham J" first="Jamie" last="Bentham">Jamie Bentham</name>
<affiliation wicri:level="3"><nlm:aff id="A9">Dept of Cardiovascular Medicine, Oxford University, Oxford</nlm:aff>
<country>Royaume-Uni</country>
<placeName><settlement type="city">Oxford</settlement>
<region type="country">Angleterre</region>
<region type="comté" nuts="2">Oxfordshire</region>
</placeName>
<wicri:orgArea>Dept of Cardiovascular Medicine, Oxford University</wicri:orgArea>
</affiliation>
</author>
<author><name sortKey="Cosgrove, Catherine" sort="Cosgrove, Catherine" uniqKey="Cosgrove C" first="Catherine" last="Cosgrove">Catherine Cosgrove</name>
<affiliation wicri:level="3"><nlm:aff id="A9">Dept of Cardiovascular Medicine, Oxford University, Oxford</nlm:aff>
<country>Royaume-Uni</country>
<placeName><settlement type="city">Oxford</settlement>
<region type="country">Angleterre</region>
<region type="comté" nuts="2">Oxfordshire</region>
</placeName>
<wicri:orgArea>Dept of Cardiovascular Medicine, Oxford University</wicri:orgArea>
</affiliation>
</author>
<author><name sortKey="Bhattacharya, Shoumo" sort="Bhattacharya, Shoumo" uniqKey="Bhattacharya S" first="Shoumo" last="Bhattacharya">Shoumo Bhattacharya</name>
<affiliation wicri:level="3"><nlm:aff id="A9">Dept of Cardiovascular Medicine, Oxford University, Oxford</nlm:aff>
<country>Royaume-Uni</country>
<placeName><settlement type="city">Oxford</settlement>
<region type="country">Angleterre</region>
<region type="comté" nuts="2">Oxfordshire</region>
</placeName>
<wicri:orgArea>Dept of Cardiovascular Medicine, Oxford University</wicri:orgArea>
</affiliation>
</author>
<author><name sortKey="Riveron, Javier Granados" sort="Riveron, Javier Granados" uniqKey="Riveron J" first="Javier Granados" last="Riveron">Javier Granados Riveron</name>
<affiliation><nlm:aff id="A10">Inst of Genetics, Nottingham University, Nottingham</nlm:aff>
<wicri:noCountry code="subfield">Nottingham</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Setchfield, Kerry" sort="Setchfield, Kerry" uniqKey="Setchfield K" first="Kerry" last="Setchfield">Kerry Setchfield</name>
<affiliation><nlm:aff id="A10">Inst of Genetics, Nottingham University, Nottingham</nlm:aff>
<wicri:noCountry code="subfield">Nottingham</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Brook, J David" sort="Brook, J David" uniqKey="Brook J" first="J. David" last="Brook">J. David Brook</name>
<affiliation><nlm:aff id="A10">Inst of Genetics, Nottingham University, Nottingham</nlm:aff>
<wicri:noCountry code="subfield">Nottingham</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Bu Lock, Frances A" sort="Bu Lock, Frances A" uniqKey="Bu Lock F" first="Frances A." last="Bu'Lock">Frances A. Bu'Lock</name>
<affiliation><nlm:aff id="A11">East Midlands Congenital Heart Centre, University Hospitals of Leicester NHS Trust, Leicester</nlm:aff>
<wicri:noCountry code="subfield">Leicester</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Thornborough, Chris" sort="Thornborough, Chris" uniqKey="Thornborough C" first="Chris" last="Thornborough">Chris Thornborough</name>
<affiliation><nlm:aff id="A11">East Midlands Congenital Heart Centre, University Hospitals of Leicester NHS Trust, Leicester</nlm:aff>
<wicri:noCountry code="subfield">Leicester</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Rahman, Thahira J" sort="Rahman, Thahira J" uniqKey="Rahman T" first="Thahira J." last="Rahman">Thahira J. Rahman</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Inst of Genetic Medicine, Newcastle Univ, Newcastle upon Tyne, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Inst of Genetic Medicine, Newcastle Univ, Newcastle upon Tyne</wicri:regionArea>
<wicri:noRegion>Newcastle upon Tyne</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Doza, Julian Palomino" sort="Doza, Julian Palomino" uniqKey="Doza J" first="Julian Palomino" last="Doza">Julian Palomino Doza</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Inst of Genetic Medicine, Newcastle Univ, Newcastle upon Tyne, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Inst of Genetic Medicine, Newcastle Univ, Newcastle upon Tyne</wicri:regionArea>
<wicri:noRegion>Newcastle upon Tyne</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Tan, Huay L" sort="Tan, Huay L" uniqKey="Tan H" first="Huay L." last="Tan">Huay L. Tan</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Inst of Genetic Medicine, Newcastle Univ, Newcastle upon Tyne, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Inst of Genetic Medicine, Newcastle Univ, Newcastle upon Tyne</wicri:regionArea>
<wicri:noRegion>Newcastle upon Tyne</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="O Sullivan, John" sort="O Sullivan, John" uniqKey="O Sullivan J" first="John" last="O'Sullivan">John O'Sullivan</name>
<affiliation><nlm:aff id="A12">Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne</nlm:aff>
<wicri:noCountry code="subfield">Newcastle upon Tyne</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Stuart, A Graham" sort="Stuart, A Graham" uniqKey="Stuart A" first="A. Graham" last="Stuart">A. Graham Stuart</name>
<affiliation wicri:level="1"><nlm:aff id="A13">Bristol Royal Hospital for Children, Bristol, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Bristol Royal Hospital for Children, Bristol</wicri:regionArea>
<wicri:noRegion>Bristol</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Blue, Gillian" sort="Blue, Gillian" uniqKey="Blue G" first="Gillian" last="Blue">Gillian Blue</name>
<affiliation wicri:level="1"><nlm:aff id="A14">The Children's Hospital at Westmead, Westmead, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>The Children's Hospital at Westmead, Westmead</wicri:regionArea>
<wicri:noRegion>Westmead</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Winlaw, David" sort="Winlaw, David" uniqKey="Winlaw D" first="David" last="Winlaw">David Winlaw</name>
<affiliation wicri:level="1"><nlm:aff id="A14">The Children's Hospital at Westmead, Westmead, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>The Children's Hospital at Westmead, Westmead</wicri:regionArea>
<wicri:noRegion>Westmead</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Postma, Alex V" sort="Postma, Alex V" uniqKey="Postma A" first="Alex V." last="Postma">Alex V. Postma</name>
<affiliation wicri:level="3"><nlm:aff id="A15">Academic Medical Center, Amsterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Academic Medical Center, Amsterdam</wicri:regionArea>
<placeName><settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mulder, Barbara J M" sort="Mulder, Barbara J M" uniqKey="Mulder B" first="Barbara J. M." last="Mulder">Barbara J. M. Mulder</name>
<affiliation wicri:level="3"><nlm:aff id="A15">Academic Medical Center, Amsterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Academic Medical Center, Amsterdam</wicri:regionArea>
<placeName><settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Zwinderman, Aelko H" sort="Zwinderman, Aelko H" uniqKey="Zwinderman A" first="Aelko H." last="Zwinderman">Aelko H. Zwinderman</name>
<affiliation wicri:level="3"><nlm:aff id="A15">Academic Medical Center, Amsterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Academic Medical Center, Amsterdam</wicri:regionArea>
<placeName><settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Van Engelen, Klaartje" sort="Van Engelen, Klaartje" uniqKey="Van Engelen K" first="Klaartje" last="Van Engelen">Klaartje Van Engelen</name>
<affiliation wicri:level="3"><nlm:aff id="A15">Academic Medical Center, Amsterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Academic Medical Center, Amsterdam</wicri:regionArea>
<placeName><settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Moorman, Antoon F M" sort="Moorman, Antoon F M" uniqKey="Moorman A" first="Antoon F. M." last="Moorman">Antoon F. M. Moorman</name>
<affiliation wicri:level="3"><nlm:aff id="A15">Academic Medical Center, Amsterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Academic Medical Center, Amsterdam</wicri:regionArea>
<placeName><settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Rauch, Anita" sort="Rauch, Anita" uniqKey="Rauch A" first="Anita" last="Rauch">Anita Rauch</name>
<affiliation wicri:level="4"><nlm:aff id="A16">Inst of Medical Genetics, University of Zurich, Switzerland</nlm:aff>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Inst of Medical Genetics, University of Zurich</wicri:regionArea>
<placeName><settlement type="city">Zurich</settlement>
<region nuts="3" type="region">Canton de Zurich</region>
</placeName>
<orgName type="university">Université de Zurich</orgName>
</affiliation>
</author>
<author><name sortKey="Gewillig, Marc" sort="Gewillig, Marc" uniqKey="Gewillig M" first="Marc" last="Gewillig">Marc Gewillig</name>
<affiliation wicri:level="1"><nlm:aff id="A17">Pediatric Cardiology, University of Leuven, Leuven, Belgium</nlm:aff>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Pediatric Cardiology, University of Leuven, Leuven</wicri:regionArea>
<wicri:noRegion>Leuven</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Breckpot, Jeroen" sort="Breckpot, Jeroen" uniqKey="Breckpot J" first="Jeroen" last="Breckpot">Jeroen Breckpot</name>
<affiliation wicri:level="1"><nlm:aff id="A18">Center for Human Genetics, Univ of Leuven, Leuven, Belgium</nlm:aff>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Center for Human Genetics, Univ of Leuven, Leuven</wicri:regionArea>
<wicri:noRegion>Leuven</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Devriendt, Koen" sort="Devriendt, Koen" uniqKey="Devriendt K" first="Koen" last="Devriendt">Koen Devriendt</name>
<affiliation wicri:level="1"><nlm:aff id="A18">Center for Human Genetics, Univ of Leuven, Leuven, Belgium</nlm:aff>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Center for Human Genetics, Univ of Leuven, Leuven</wicri:regionArea>
<wicri:noRegion>Leuven</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Lathrop, G Mark" sort="Lathrop, G Mark" uniqKey="Lathrop G" first="G. Mark" last="Lathrop">G. Mark Lathrop</name>
<affiliation><nlm:aff id="A7">Commisariat àl'énergie Atomique (CEA), Institut Genomique, Centre National de Genotypage, Evry</nlm:aff>
<wicri:noCountry code="subfield">Evry</wicri:noCountry>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A8">Fondation Jean Dausset, Centre d'Etude du Polymorphism Human, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Fondation Jean Dausset, Centre d'Etude du Polymorphism Human, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Farrall, Martin" sort="Farrall, Martin" uniqKey="Farrall M" first="Martin" last="Farrall">Martin Farrall</name>
<affiliation wicri:level="3"><nlm:aff id="A9">Dept of Cardiovascular Medicine, Oxford University, Oxford</nlm:aff>
<country>Royaume-Uni</country>
<placeName><settlement type="city">Oxford</settlement>
<region type="country">Angleterre</region>
<region type="comté" nuts="2">Oxfordshire</region>
</placeName>
<wicri:orgArea>Dept of Cardiovascular Medicine, Oxford University</wicri:orgArea>
</affiliation>
</author>
<author><name sortKey="Goodship, Judith A" sort="Goodship, Judith A" uniqKey="Goodship J" first="Judith A." last="Goodship">Judith A. Goodship</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Inst of Genetic Medicine, Newcastle Univ, Newcastle upon Tyne, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Inst of Genetic Medicine, Newcastle Univ, Newcastle upon Tyne</wicri:regionArea>
<wicri:noRegion>Newcastle upon Tyne</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Cordell, Heather J" sort="Cordell, Heather J" uniqKey="Cordell H" first="Heather J." last="Cordell">Heather J. Cordell</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Inst of Genetic Medicine, Newcastle Univ, Newcastle upon Tyne, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Inst of Genetic Medicine, Newcastle Univ, Newcastle upon Tyne</wicri:regionArea>
<wicri:noRegion>Newcastle upon Tyne</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Brody, Lawrence C" sort="Brody, Lawrence C" uniqKey="Brody L" first="Lawrence C." last="Brody">Lawrence C. Brody</name>
<affiliation><nlm:aff id="A2">Molecular Pathogenesis Section, Genome Technology Branch, National Human Genome Research Inst</nlm:aff>
<wicri:noCountry code="subfield">National Human Genome Research Inst</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Keavney, Bernard D" sort="Keavney, Bernard D" uniqKey="Keavney B" first="Bernard D." last="Keavney">Bernard D. Keavney</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Inst of Genetic Medicine, Newcastle Univ, Newcastle upon Tyne, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Inst of Genetic Medicine, Newcastle Univ, Newcastle upon Tyne</wicri:regionArea>
<wicri:noRegion>Newcastle upon Tyne</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A19">Institute of Cardiovascular Sciences, The Univ of Manchester, Manchester, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Institute of Cardiovascular Sciences, The Univ of Manchester, Manchester</wicri:regionArea>
<placeName><settlement type="city">Manchester</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Manchester</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">Circulation. Cardiovascular genetics</title>
<idno type="ISSN">1942-325X</idno>
<idno type="eISSN">1942-3268</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">Association between the C677T polymorphism of the methylene tetrahydrofolate reductase (<italic>MTHFR</italic>
) gene and congenital heart disease (CHD) is contentious.</p>
</sec>
<sec id="S2"><title>Methods and Results</title>
<p id="P2">We compared genotypes between CHD cases and controls, and between mothers of CHD cases and controls. We placed our results in context by conducting metaanalyses of previously published studies. Among 5,814 cases with primary genotype data and 10,056 controls, there was no evidence of association between <italic>MTHFR</italic>
 C677T genotype and CHD risk (OR 0.96 [95% CI 0.87-1.07]). A random-effects meta-analysis of all studies (involving 7,697 cases and 13,125 controls) suggested the presence of association (OR 1.25 [95% CI 1.03-1.51]; p=0.022), but with substantial heterogeneity among contributing studies (I<sup>2</sup>
=64.4%), and evidence of publication bias. Meta-analysis of large studies only (defined by a variance of the log OR less than 0.05), which together contributed 83% of all cases, yielded no evidence of association (OR 0.97 [95% CI 0.91-1.03]), without significant heterogeneity (I<sup>2</sup>
=0). Moreover, meta-analysis of 1,781 mothers of CHD cases (829 of whom were genotyped in this study) and 19,861 controls revealed no evidence of association between maternal C677T genotype and risk of CHD in offspring (OR 1.13 [95% CI 0.87-1.47]). There was no significant association between <italic>MTHFR</italic>
 genotype and CHD risk in large studies from regions with different levels of dietary folate.</p>
</sec>
<sec id="S3"><title>Conclusions</title>
<p id="P3">The <italic>MTHFR</italic>
 C677T polymorphism, which directly influences plasma folate levels, is not associated with CHD risk. Publication biases appear to substantially contaminate the literature with regard to this genetic association.</p>
</sec>
</div>
</front>
</TEI>
<affiliations><list><country><li>Australie</li>
<li>Belgique</li>
<li>France</li>
<li>Pays-Bas</li>
<li>Royaume-Uni</li>
<li>Suisse</li>
<li>États-Unis</li>
</country>
<region><li>Angleterre</li>
<li>Canton de Zurich</li>
<li>Grand Manchester</li>
<li>Hollande-Septentrionale</li>
<li>Maryland</li>
<li>Michigan</li>
<li>Oxfordshire</li>
<li>État de New York</li>
<li>Île-de-France</li>
</region>
<settlement><li>Amsterdam</li>
<li>Manchester</li>
<li>Oxford</li>
<li>Paris</li>
<li>Zurich</li>
</settlement>
<orgName><li>Université de Zurich</li>
</orgName>
</list>
<tree><noCountry><name sortKey="Brody, Lawrence C" sort="Brody, Lawrence C" uniqKey="Brody L" first="Lawrence C." last="Brody">Lawrence C. Brody</name>
<name sortKey="Brook, J David" sort="Brook, J David" uniqKey="Brook J" first="J. David" last="Brook">J. David Brook</name>
<name sortKey="Bu Lock, Frances A" sort="Bu Lock, Frances A" uniqKey="Bu Lock F" first="Frances A." last="Bu'Lock">Frances A. Bu'Lock</name>
<name sortKey="Druschel, Charlotte" sort="Druschel, Charlotte" uniqKey="Druschel C" first="Charlotte" last="Druschel">Charlotte Druschel</name>
<name sortKey="O Sullivan, John" sort="O Sullivan, John" uniqKey="O Sullivan J" first="John" last="O'Sullivan">John O'Sullivan</name>
<name sortKey="Pangilinan, Faith" sort="Pangilinan, Faith" uniqKey="Pangilinan F" first="Faith" last="Pangilinan">Faith Pangilinan</name>
<name sortKey="Prentice, R Reid" sort="Prentice, R Reid" uniqKey="Prentice R" first="R. Reid" last="Prentice">R. Reid Prentice</name>
<name sortKey="Riveron, Javier Granados" sort="Riveron, Javier Granados" uniqKey="Riveron J" first="Javier Granados" last="Riveron">Javier Granados Riveron</name>
<name sortKey="Setchfield, Kerry" sort="Setchfield, Kerry" uniqKey="Setchfield K" first="Kerry" last="Setchfield">Kerry Setchfield</name>
<name sortKey="Thornborough, Chris" sort="Thornborough, Chris" uniqKey="Thornborough C" first="Chris" last="Thornborough">Chris Thornborough</name>
</noCountry>
<country name="Royaume-Uni"><noRegion><name sortKey="Mamasoula, Chrysovalanto" sort="Mamasoula, Chrysovalanto" uniqKey="Mamasoula C" first="Chrysovalanto" last="Mamasoula">Chrysovalanto Mamasoula</name>
</noRegion>
<name sortKey="Bentham, Jamie" sort="Bentham, Jamie" uniqKey="Bentham J" first="Jamie" last="Bentham">Jamie Bentham</name>
<name sortKey="Bhattacharya, Shoumo" sort="Bhattacharya, Shoumo" uniqKey="Bhattacharya S" first="Shoumo" last="Bhattacharya">Shoumo Bhattacharya</name>
<name sortKey="Brown, Danielle L" sort="Brown, Danielle L" uniqKey="Brown D" first="Danielle L." last="Brown">Danielle L. Brown</name>
<name sortKey="Cordell, Heather J" sort="Cordell, Heather J" uniqKey="Cordell H" first="Heather J." last="Cordell">Heather J. Cordell</name>
<name sortKey="Cosgrove, Catherine" sort="Cosgrove, Catherine" uniqKey="Cosgrove C" first="Catherine" last="Cosgrove">Catherine Cosgrove</name>
<name sortKey="Doza, Julian Palomino" sort="Doza, Julian Palomino" uniqKey="Doza J" first="Julian Palomino" last="Doza">Julian Palomino Doza</name>
<name sortKey="Farrall, Martin" sort="Farrall, Martin" uniqKey="Farrall M" first="Martin" last="Farrall">Martin Farrall</name>
<name sortKey="Goodship, Judith A" sort="Goodship, Judith A" uniqKey="Goodship J" first="Judith A." last="Goodship">Judith A. Goodship</name>
<name sortKey="Hall, Darroch" sort="Hall, Darroch" uniqKey="Hall D" first="Darroch" last="Hall">Darroch Hall</name>
<name sortKey="Keavney, Bernard D" sort="Keavney, Bernard D" uniqKey="Keavney B" first="Bernard D." last="Keavney">Bernard D. Keavney</name>
<name sortKey="Keavney, Bernard D" sort="Keavney, Bernard D" uniqKey="Keavney B" first="Bernard D." last="Keavney">Bernard D. Keavney</name>
<name sortKey="Pierscionek, Tomasz" sort="Pierscionek, Tomasz" uniqKey="Pierscionek T" first="Tomasz" last="Pierscionek">Tomasz Pierscionek</name>
<name sortKey="Rahman, Thahira J" sort="Rahman, Thahira J" uniqKey="Rahman T" first="Thahira J." last="Rahman">Thahira J. Rahman</name>
<name sortKey="Stuart, A Graham" sort="Stuart, A Graham" uniqKey="Stuart A" first="A. Graham" last="Stuart">A. Graham Stuart</name>
<name sortKey="Tan, Huay L" sort="Tan, Huay L" uniqKey="Tan H" first="Huay L." last="Tan">Huay L. Tan</name>
<name sortKey="Topf, Ana" sort="Topf, Ana" uniqKey="Topf A" first="Ana" last="Töpf">Ana Töpf</name>
</country>
<country name="États-Unis"><region name="Maryland"><name sortKey="Mills, James L" sort="Mills, James L" uniqKey="Mills J" first="James L." last="Mills">James L. Mills</name>
</region>
<name sortKey="Pass, Kenneth" sort="Pass, Kenneth" uniqKey="Pass K" first="Kenneth" last="Pass">Kenneth Pass</name>
<name sortKey="Russell, Mark W" sort="Russell, Mark W" uniqKey="Russell M" first="Mark W." last="Russell">Mark W. Russell</name>
</country>
<country name="France"><region name="Île-de-France"><name sortKey="Zelenika, Diana" sort="Zelenika, Diana" uniqKey="Zelenika D" first="Diana" last="Zelenika">Diana Zelenika</name>
</region>
<name sortKey="Lathrop, G Mark" sort="Lathrop, G Mark" uniqKey="Lathrop G" first="G. Mark" last="Lathrop">G. Mark Lathrop</name>
</country>
<country name="Australie"><noRegion><name sortKey="Blue, Gillian" sort="Blue, Gillian" uniqKey="Blue G" first="Gillian" last="Blue">Gillian Blue</name>
</noRegion>
<name sortKey="Winlaw, David" sort="Winlaw, David" uniqKey="Winlaw D" first="David" last="Winlaw">David Winlaw</name>
</country>
<country name="Pays-Bas"><region name="Hollande-Septentrionale"><name sortKey="Postma, Alex V" sort="Postma, Alex V" uniqKey="Postma A" first="Alex V." last="Postma">Alex V. Postma</name>
</region>
<name sortKey="Moorman, Antoon F M" sort="Moorman, Antoon F M" uniqKey="Moorman A" first="Antoon F. M." last="Moorman">Antoon F. M. Moorman</name>
<name sortKey="Mulder, Barbara J M" sort="Mulder, Barbara J M" uniqKey="Mulder B" first="Barbara J. M." last="Mulder">Barbara J. M. Mulder</name>
<name sortKey="Van Engelen, Klaartje" sort="Van Engelen, Klaartje" uniqKey="Van Engelen K" first="Klaartje" last="Van Engelen">Klaartje Van Engelen</name>
<name sortKey="Zwinderman, Aelko H" sort="Zwinderman, Aelko H" uniqKey="Zwinderman A" first="Aelko H." last="Zwinderman">Aelko H. Zwinderman</name>
</country>
<country name="Suisse"><region name="Canton de Zurich"><name sortKey="Rauch, Anita" sort="Rauch, Anita" uniqKey="Rauch A" first="Anita" last="Rauch">Anita Rauch</name>
</region>
</country>
<country name="Belgique"><noRegion><name sortKey="Gewillig, Marc" sort="Gewillig, Marc" uniqKey="Gewillig M" first="Marc" last="Gewillig">Marc Gewillig</name>
</noRegion>
<name sortKey="Breckpot, Jeroen" sort="Breckpot, Jeroen" uniqKey="Breckpot J" first="Jeroen" last="Breckpot">Jeroen Breckpot</name>
<name sortKey="Devriendt, Koen" sort="Devriendt, Koen" uniqKey="Devriendt K" first="Koen" last="Devriendt">Koen Devriendt</name>
</country>
</tree>
</affiliations>
</record>

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Association between C677T Polymorphism of Methylene Tetrahydrofolate Reductase and Congenital Heart Disease: Meta-Analysis of 7,697 Cases and 13,125 Controls

Association between C677T Polymorphism of Methylene Tetrahydrofolate Reductase and Congenital Heart Disease: Meta-Analysis of 7,697 Cases and 13,125 Controls

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