{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:05:18Z","timestamp":1792785918369,"version":"4.5.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"20","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370350"],"award-info":[{"award-number":["82370350"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82300340"],"award-info":[{"award-number":["82300340"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Internal Fund from TEDA International Cardiovascular Hospital","award":["2021-ZX-002"],"award-info":[{"award-number":["2021-ZX-002"]}],"id":[{"id":"https:\/\/ror.org\/0247xav12","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Tianjin Key Medical Discipline Construction Project","award":["TJYXZDXK-3-036C"],"award-info":[{"award-number":["TJYXZDXK-3-036C"]}]},{"name":"Special Fund for High Quality Development Project"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Patent ductus arteriosus (PDA) is a common congenital heart disease (CHD) with a complex genetic basis. The transcription factor MEF2C plays a critical role in cardiac development, but the role of promoter region variants in PDA has not been explored. This study aimed to identify MEF2C promoter variants in PDA patients and investigate their functional consequences. We sequenced the MEF2C promoter region in 318 children with PDA and 306 healthy controls. Identified variants were subjected to dual-luciferase reporter assays in A7r5 vascular smooth muscle cells to assess transcriptional activity. Bioinformatics (JASPAR) and electrophoretic mobility shift assays (EMSA) were used to predict and validate changes in transcription factor binding. Seventeen variants were identified, of which seven were present exclusively in PDA patients. Three variants were novel. Dual-luciferase assays showed that six variants significantly altered promoter activity compared to wild-type (range 69.6%\u201382.3%). JASPAR prediction revealed that these variants affected binding sites for 16 transcription factors, including GATA1, GATA2, GATA3, STAT3, ZEB1 and E2F1. EMSA confirmed altered DNA-protein binding patterns for all six variants, and super-shift assays further validated that the g.24571 A\u2009&amp;gt;\u2009G variant specifically disrupts GATA3 binding. This is the first study to identify functionally relevant MEF2C promoter variants in PDA. Our findings suggest that dysregulation of MEF2C through promoter variants may contribute to PDA pathogenesis by disrupting critical transcription factor interactions. These results extend the genetic landscape of PDA beyond coding regions and provide new insights into the molecular mechanisms of CHD.<\/jats:p>","DOI":"10.1093\/hmg\/ddag097","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T12:06:48Z","timestamp":1789474008000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>MEF2C<\/i>\n                    promoter variants in patent ductus arteriosus: a genetic and functional study"],"prefix":"10.1093","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7813-0679","authenticated-orcid":false,"given":"Shao-Jie","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery & The Institute of Cardiovascular Diseases, TEDA International Cardiovascular Hospital, Tianjin University , No. 61, 3rd Ave, TEDA, Tianjin 300457, \u00a0","place":["China"]},{"name":"Graduate School, Chengde Medical University , Anyuan Road, Shuangqiao District, Chengde 067000, \u00a0","place":["China"]},{"name":"Tianjin Key Laboratory of Molecular Regulation of Cardiovascular Diseases and Translational Medicine , No. 61, 3rd Ave, TEDA, Tianjin 300457 ,","place":["China"]},{"name":"TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences , No. 61, 3rd Ave, TEDA, Tianjin 300457, \u00a0","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2695-8239","authenticated-orcid":false,"given":"Huan-Xin","family":"Chen","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Molecular Regulation of Cardiovascular Diseases and Translational Medicine , No. 61, 3rd Ave, TEDA, Tianjin 300457 ,","place":["China"]},{"name":"TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences , No. 61, 3rd Ave, TEDA, Tianjin 300457, \u00a0","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9792-4431","authenticated-orcid":false,"given":"Qin","family":"Yang","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Molecular Regulation of Cardiovascular Diseases and Translational Medicine , No. 61, 3rd Ave, TEDA, Tianjin 300457 ,","place":["China"]},{"name":"TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences , No. 61, 3rd Ave, TEDA, Tianjin 300457, \u00a0","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6497-876X","authenticated-orcid":false,"given":"Guo-Wei","family":"He","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery & The Institute of Cardiovascular Diseases, TEDA International Cardiovascular Hospital, Tianjin University , No. 61, 3rd Ave, TEDA, Tianjin 300457, \u00a0","place":["China"]},{"name":"Graduate School, Chengde Medical University , Anyuan Road, Shuangqiao District, Chengde 067000, \u00a0","place":["China"]},{"name":"Tianjin Key Laboratory of Molecular Regulation of Cardiovascular Diseases and Translational Medicine , No. 61, 3rd Ave, TEDA, Tianjin 300457 ,","place":["China"]},{"name":"TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences , No. 61, 3rd Ave, TEDA, Tianjin 300457, \u00a0","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,26]]},"reference":[{"key":"2026092608232792300_ref1","doi-asserted-by":"publisher","first-page":"562","DOI":"10.3390\/jpm11060562","article-title":"Personalized genetic diagnosis of congenital heart defects in newborns","volume":"11","author":"Diz","year":"2021","journal-title":"J Pers Med"},{"key":"2026092608232792300_ref2","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1001\/jamapediatrics.2015.0987","article-title":"Diagnosis, evaluation, and Management of Patent Ductus Arteriosus in preterm neonates","volume":"169","author":"Jain","year":"2015","journal-title":"JAMA Pediatr"},{"key":"2026092608232792300_ref3","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.631","article-title":"Congenital heart disease: types, pathophysiology, diagnosis, and treatment options","volume":"5","author":"Meng","year":"2024","journal-title":"MedComm."},{"key":"2026092608232792300_ref4","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2020.590578","article-title":"Management of Patent Ductus Arteriosus in premature infants in 2020","volume":"8","author":"Parkerson","year":"2020","journal-title":"Front Pediatr"},{"key":"2026092608232792300_ref5","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1016\/j.jpeds.2008.05.059","article-title":"Prevalence of congenital heart defects in metropolitan Atlanta, 1998-2005","volume":"153","author":"Reller","year":"2008","journal-title":"J 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