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Although the coding region of <jats:italic>MEF2C<\/jats:italic> is highly relevant to cardiac malformations, the role of <jats:italic>MEF2C<\/jats:italic> gene promoter variants in VSD patients has not been genetically investigated. We investigated the role of <jats:italic>MEF2C<\/jats:italic> gene promoter variants in 400 Han Chinese subjects (200 patients with isolated and sporadic VSD and 200 healthy controls). The promoter region of the <jats:italic>MEF2C<\/jats:italic> gene was sequenced that identified 10 variants. Expression vectors encompassing the variants and the firefly luciferase reporter gene plasmid (pGL3\u2010basic) were constructed and subsequently transfected into HEK\u2010293 cells. The luciferase activities were measured by Dual\u2010luciferase reporter assay system. <jats:italic>MEF2C<\/jats:italic> gene promoter transcriptional activity was significantly reduced in 4 of the 10 variants in HEK\u2010293 cells (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). In addition, the JASPAR database was used to perform bioinformatics analysis, which showed that these variants disrupt the putative binding sites of transcription factors and affected the expression of <jats:italic>MEF2C<\/jats:italic> protein. This study for the first time identified the variants in the promoter of the <jats:italic>MEF2C<\/jats:italic> gene in Han Chinese population and revealed the role of these variants in the formation of VSD.<\/jats:p>","DOI":"10.1002\/ajmg.a.62871","type":"journal-article","created":{"date-parts":[[2022,6,20]],"date-time":"2022-06-20T07:44:57Z","timestamp":1655711097000},"page":"2397-2405","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Functional significance of novel variants of the <scp><i>MEF2C<\/i><\/scp> gene promoter in congenital ventricular septal defects"],"prefix":"10.1002","volume":"188","author":[{"given":"Zhi\u2010Hua","family":"Zeng","sequence":"first","affiliation":[{"name":"The Institute of Cardiovascualr Diseases &amp; Department of Cardiovascular surgery TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences &amp; Graduate School of Peking Union Medical College &amp; Tianjin University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan\u2010Xin","family":"Chen","sequence":"additional","affiliation":[{"name":"The Institute of Cardiovascualr Diseases &amp; Department of Cardiovascular surgery TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences &amp; Graduate School of Peking Union Medical College &amp; Tianjin University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010Cheng","family":"Liu","sequence":"additional","affiliation":[{"name":"The Institute of Cardiovascualr Diseases &amp; Department of Cardiovascular surgery TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences &amp; Graduate School of Peking Union Medical College &amp; Tianjin University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Yang","sequence":"additional","affiliation":[{"name":"The Institute of Cardiovascualr Diseases &amp; Department of Cardiovascular surgery TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences &amp; Graduate School of Peking Union Medical College &amp; Tianjin University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6497-876X","authenticated-orcid":false,"given":"Guo\u2010Wei","family":"He","sequence":"additional","affiliation":[{"name":"The Institute of Cardiovascualr Diseases &amp; Department of Cardiovascular surgery TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences &amp; Graduate School of Peking Union Medical College &amp; Tianjin University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,6,20]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.126383"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2007.01.001"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.15950"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2017.04.011"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2008.120931"},{"issue":"9","key":"e_1_2_13_7_1","first-page":"972","article-title":"Discovery and functional analysis of a novel ISL1 variant associated with congenital heart defect","volume":"37","author":"Dong B.","year":"2020","journal-title":"Zhonghua Yi Xue Yi Chuan Xue Za Zhi"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz1001"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carpath.2009.06.008"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1801562"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-11-1389"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw1064"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5317.1404"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00246-018-1822-y"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.008396"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60355-4"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.21353"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jped.2019.07.004"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.09.003"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2011.08.025"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2009.08.046"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00513-19"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3101"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp532"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.309140"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.16218"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00167.2021"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62871","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.62871","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62871","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T06:15:47Z","timestamp":1692857747000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.62871"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,20]]},"references-count":26,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2022,8]]}},"alternative-id":["10.1002\/ajmg.a.62871"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.62871","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,20]]},"assertion":[{"value":"2021-12-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}