{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:01:37Z","timestamp":1753869697361,"version":"3.41.2"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T00:00:00Z","timestamp":1705536000000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870279"],"award-info":[{"award-number":["81870279"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Dilated cardiomyopathy (DCM) is a major cause of heart failure and sudden cardiac death. As DCM is a genetically heterogeneous disease, genetic variants of cardiac transcription factor genes may play an important role. Transcription factor TBX20, an indispensable factor in normal heart development, is involved in the regulation of cardiac structure and function. Although the <jats:italic>TBX20<\/jats:italic> gene is associated with the occurrence and development of DCM, the influence of genetic variants of the <jats:italic>TBX20<\/jats:italic> gene promoter region on DCM has not been reported.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a case\u2013control study consisting of 107 DCM patients and 210 healthy controls. Genetic variants within <jats:italic>TBX20<\/jats:italic> gene promoter region were identified using sequencing techniques and were functionally analyzed by dual\u2010luciferase reporting assay. Electrophoretic mobility shift assay (EMSA) was used to investigate DNA\u2010protein interactions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In this study cohort (<jats:italic>n<\/jats:italic>\u2009=\u2009317), we identified eight variants within <jats:italic>TBX20<\/jats:italic> gene promoter. One novel DNA sequence variants (DSV) (g.4275G&gt;T) and four single\u2010nucleotide polymorphisms (SNPs) [g.4169G&gt;A (rs1263874255), g.4949C&gt;T (rs1191745927), g.5114G&gt;A (rs112076877), g.5252C&gt;T (rs1356932911)] were identified in DCM patients, but in none of controls. Among them, the DSV (g.4275G&gt;T) and three SNPs [g.4949C&gt;T (rs1191745927), g.5114G&gt;A (rs112076877) and g.5252C&gt;T (rs1356932911)] significantly altered the transcription activity of <jats:italic>TBX20<\/jats:italic> gene promoter by dual\u2010luciferase reporting assay (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Further, EMSA assay indicated that the DSV (g.4275G&gt;T) and three SNPs [g.4949C&gt;T (rs1191745927), g.5114G&gt;A (rs112076877) and g.5252C&gt;T (rs1356932911)] affected the binding of transcription factors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These data indicate that the DSV (g.4275G&gt;T) and three SNPs [g.4949C&gt;T (rs1191745927), g.5114G&gt;A (rs112076877) and g.5252C&gt;T (rs1356932911)] increase transcription activity of <jats:italic>TBX20<\/jats:italic> gene promoter in both HEK\u2010293 and neonatal rat cardiomyocytes (NRCMs) cell lines by affecting the binding of transcription factors. But the mechanism remains to be verified in\u00a0vivo.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2355","type":"journal-article","created":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T12:04:23Z","timestamp":1705579463000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genetic and functional variants of the <i>TBX20<\/i> gene promoter in dilated cardiomyopathy"],"prefix":"10.1002","volume":"12","author":[{"given":"Xue","family":"Gao","sequence":"first","affiliation":[{"name":"Cheeloo College of Medicine Shandong University  Jinan Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuchao","family":"Pang","sequence":"additional","affiliation":[{"name":"The Center for Molecular Genetics of Cardiovascular Diseases Affiliated Hospital of Jining Medical University, Jining Medical University  Jining Shandong China"},{"name":"Shandong Provincial Sino\u2010US Cooperation Research Center for Translational Medicine Affiliated Hospital of Jining Medical University, Jining Medical University  Jining Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liangcai","family":"Ding","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine Yanzhou People's Hospital, Jining Medical University  Jining Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han","family":"Yan","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine Yanzhou People's Hospital, Jining Medical University  Jining Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yinghua","family":"Cui","sequence":"additional","affiliation":[{"name":"Division of Cardiology Affiliated Hospital of Jining Medical University, Jining Medical University  Jining Shandong 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