{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T11:21:14Z","timestamp":1773314474476,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2014,9,8]],"date-time":"2014-09-08T00:00:00Z","timestamp":1410134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Basic Research Program of China","doi-asserted-by":"crossref","award":["2010CB529504"],"award-info":[{"award-number":["2010CB529504"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["30930096"],"award-info":[{"award-number":["30930096"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:p>Background: Tetralogy of Fallot (ToF) is the most common form of cyanotic congenital heart disease and is a major cause of significant morbidity and mortality. <jats:italic>VANGL2<\/jats:italic> is a critical gene in the planar cell polarity pathway that plays an important role in the development of the heart. This study investigates the methylation status of the promoter region of <jats:italic>VANGL2<\/jats:italic> and the expression pattern of <jats:italic>VANGL2<\/jats:italic> in cardiac tissue. Methods: The promoter region of <jats:italic>VANGL2<\/jats:italic> was sequenced in 200 ToF patients and 400 control subjects. Methylation levels were measured in four regions of the <jats:italic>VANGL2<\/jats:italic> promoter (B1\u20101: \u2212282 bp \u223c \u2212117 bp, B1\u20132: \u2212117 bp \u223c 41 bp, B2: 8 bp \u223c 157 bp, B3: 132 bp \u223c 401 bp) by bisulfite sequencing PCR in the right ventricular outflow tract of the myocardium. Quantitative real\u2010time PCR and immunohistochemistry were used to detect the mRNA and protein expression levels, respectively. Results: No mutations were found in the promoter region, but two SNPs (rs11582932 T&gt;G, rs11265385 T&gt;G) were found in ToF patients and controls with similar frequencies (<jats:italic>p<\/jats:italic>\u2009&gt;\u20090.05). The overall methylation status of the <jats:italic>VANGL2<\/jats:italic> promoter was significantly higher in ToF patients than in controls (<jats:italic>p<\/jats:italic>\u2009=\u20090.0234). Specifically, the methylation levels of regions B1\u20101 and B3 were significantly higher in ToF patients (<jats:italic>p<\/jats:italic>\u2009=\u20090.0042, <jats:italic>p<\/jats:italic>\u2009=\u20090.0418). Both the <jats:italic>VANGL2<\/jats:italic> mRNA and protein levels were significantly lower in ToF patients than in controls (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Conclusion: The aberrant <jats:italic>VANGL2<\/jats:italic> promoter methylation and the decreased gene expression in ToF patients may provide important clues for the development of ToF. Birth Defects Research (Part A) 100:973\u2013984, 2014. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/bdra.23291","type":"journal-article","created":{"date-parts":[[2014,9,8]],"date-time":"2014-09-08T15:17:05Z","timestamp":1410189425000},"page":"973-984","source":"Crossref","is-referenced-by-count":20,"title":["Promoter methylation and expression of the <i>VANGL2<\/i> gene in the myocardium of pediatric patients with Tetralogy of Fallot"],"prefix":"10.1002","volume":"100","author":[{"given":"Yuan","family":"Yuan","sequence":"first","affiliation":[{"name":"Children's Hospital of Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Gao","sequence":"additional","affiliation":[{"name":"Children's Hospital of Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huijun","family":"Wang","sequence":"additional","affiliation":[{"name":"Children's Hospital of Fudan University 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