{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T21:10:18Z","timestamp":1770412218902,"version":"3.49.0"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,8,18]],"date-time":"2014-08-18T00:00:00Z","timestamp":1408320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004826","name":"Beijing Natural Science Foundation","doi-asserted-by":"crossref","award":["7132036"],"award-info":[{"award-number":["7132036"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Fund of China","doi-asserted-by":"crossref","award":["81370967\/ H0724, 81270699\/H0417, 81102117\/H260"],"award-info":[{"award-number":["81370967\/ H0724, 81270699\/H0417, 81102117\/H260"]}],"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":[[2015,1]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Animal models of neural tube defects (NTDs) have indicated roles for the <jats:italic>Fzd3<\/jats:italic> gene and the planar cell polarity signaling pathway in convergent extension. We investigated the involvement of <jats:italic>FZD3<\/jats:italic> in genetic and epigenetic mechanisms associated with human NTDs, especially spina bifida. We explored the effects of variants spanning the <jats:italic>FZD3<\/jats:italic> gene in NTDs and examined the role of aberrant methylation of the <jats:italic>FZD3<\/jats:italic> promoter on gene expression in brain tissue in spina bifida.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Six <jats:italic>FZD3<\/jats:italic> single nucleotide polymorphisms were genotyped using a MassARRAY system in tissue from 165 NTD fetuses and 152 controls. DNA methylation aberrations in the <jats:italic>FZD3<\/jats:italic> promoter region were detected using a MassARRAY EpiTYPER (17 CpG units from \u2212500 to \u22122400 bp from the transcription start site) in brain tissue from 77 spina bifida and 74 control fetuses.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>None of the six single nucleotide polymorphisms evaluated were significantly associated with spina bifida, but the mean methylation level was significantly higher in spina bifida samples (13.70%) compared with control samples (10.91%) (<jats:italic>p<\/jats:italic>\u2009=\u20090.001). In terms of specific sites, DNA methylation levels were significantly higher in the spina bifida samples at 14 of the 17 CpG units, which mostly included in R2 region. <jats:italic>FZD3<\/jats:italic> mRNA expression was negatively correlated with methylation of the <jats:italic>FZD3<\/jats:italic> promoter region, especially the R2 region (R\u2009=\u20090.970; <jats:italic>p<\/jats:italic>\u2009=\u20090.001) in HeLa cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>The results of this study suggest that DNA methylation plays an important role in <jats:italic>FZD3<\/jats:italic> gene expression regulation and may be associated with an increased risk of spina bifida. Birth Defects Research (Part A) 103:37\u201344, 2015. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdra.23285","type":"journal-article","created":{"date-parts":[[2014,8,18]],"date-time":"2014-08-18T05:29:32Z","timestamp":1408339772000},"page":"37-44","source":"Crossref","is-referenced-by-count":13,"title":["DNA methylation aberrations rather than polymorphisms of <i>FZD3<\/i> gene increase the risk of spina bifida in a high\u2010risk region for neural tube defects"],"prefix":"10.1002","volume":"103","author":[{"given":"Shaofang","family":"Shangguan","sequence":"first","affiliation":[{"name":"Beijing Municipal Key Laboratory of Child Development and Nutriomics Capital Institute of Pediatrics  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing Municipal Key Laboratory of Child Development and Nutriomics Capital Institute of Pediatrics  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaoyan","family":"Chang","sequence":"additional","affiliation":[{"name":"Beijing Municipal Key Laboratory of Child Development and Nutriomics Capital Institute of Pediatrics  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoling","family":"Lu","sequence":"additional","affiliation":[{"name":"Beijing Municipal Key Laboratory of Child Development and Nutriomics Capital Institute of Pediatrics  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing Municipal Key Laboratory of Child Development and Nutriomics Capital Institute of Pediatrics  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lihua","family":"Wu","sequence":"additional","affiliation":[{"name":"Beijing Municipal Key Laboratory of Child Development and Nutriomics Capital Institute of Pediatrics  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianhua","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Capital Institute of Pediatrics  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiuwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Capital Institute of Pediatrics  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Capital Institute of Pediatrics  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yihua","family":"Bao","sequence":"additional","affiliation":[{"name":"Beijing Municipal Key Laboratory of Child Development and Nutriomics Capital Institute of Pediatrics  Beijing 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