Pathophysiological Role of Variants of the Promoter Region of CITED2 Gene in Sporadic Tetralogy of Fallot Patients with Cellular Function Verification
Tetralogy of Fallot (TOF) is a common congenital heart malformation. Genetic variants in the CITED2 coding region are known to be significantly associated with cardiac malformation, but the role of variants in the CITED2 promoter region in the development of TOF remains unclear. In this study, we in...
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MDPI AG
2022-11-01
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| author | Zhuo Chen Huan-Xin Chen Hai-Tao Hou Xiu-Yun Yin Qin Yang Guo-Wei He |
| author_facet | Zhuo Chen Huan-Xin Chen Hai-Tao Hou Xiu-Yun Yin Qin Yang Guo-Wei He |
| author_sort | Zhuo Chen |
| collection | DOAJ |
| description | Tetralogy of Fallot (TOF) is a common congenital heart malformation. Genetic variants in the CITED2 coding region are known to be significantly associated with cardiac malformation, but the role of variants in the CITED2 promoter region in the development of TOF remains unclear. In this study, we investigated CITED2 promoter variants in the DNA of 605 subjects, including 312 TOF patients and 293 unrelated healthy controls, by Sanger sequencing. We identified nine CITED2 gene promoter variants (including one novel heterozygous variant). Six were found only in patients with TOF and none in the control group. The transcriptional activity of the CITED2 gene promoter in mouse cardiomyocyte (HL-1) cells was significantly altered by the six variants (<i>p</i> < 0.05). The results of the electrophoretic mobility change assay and JASPAR database analysis showed that these variants generated or destroyed a series of possible transcription factor binding sites, resulting in changes in the CITED2 protein expression. We conclude that CITED2 promoter variants in TOF patients affect transcriptional activity and may be involved in the occurrence and progression of TOF. These findings may provide new insights into molecular pathogenesis and potential therapeutic insights in patients with TOF. |
| first_indexed | 2024-03-09T19:14:40Z |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-09T19:14:40Z |
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| spelling | doaj.art-e2b3b76817824adc8353c1f0387b310d2023-11-24T03:53:55ZengMDPI AGBiomolecules2218-273X2022-11-011211164410.3390/biom12111644Pathophysiological Role of Variants of the Promoter Region of CITED2 Gene in Sporadic Tetralogy of Fallot Patients with Cellular Function VerificationZhuo Chen0Huan-Xin Chen1Hai-Tao Hou2Xiu-Yun Yin3Qin Yang4Guo-Wei He5The Institute of Cardiovascular Diseases & Department Cardiovascular Surgery, TEDA International Cardiovascular Hospital, Tianjin University & Chinese Academy of Medical Sciences, Tianjin 300457, ChinaThe Institute of Cardiovascular Diseases & Department Cardiovascular Surgery, TEDA International Cardiovascular Hospital, Tianjin University & Chinese Academy of Medical Sciences, Tianjin 300457, ChinaThe Institute of Cardiovascular Diseases & Department Cardiovascular Surgery, TEDA International Cardiovascular Hospital, Tianjin University & Chinese Academy of Medical Sciences, Tianjin 300457, ChinaThe Institute of Cardiovascular Diseases & Department Cardiovascular Surgery, TEDA International Cardiovascular Hospital, Tianjin University & Chinese Academy of Medical Sciences, Tianjin 300457, ChinaThe Institute of Cardiovascular Diseases & Department Cardiovascular Surgery, TEDA International Cardiovascular Hospital, Tianjin University & Chinese Academy of Medical Sciences, Tianjin 300457, ChinaThe Institute of Cardiovascular Diseases & Department Cardiovascular Surgery, TEDA International Cardiovascular Hospital, Tianjin University & Chinese Academy of Medical Sciences, Tianjin 300457, ChinaTetralogy of Fallot (TOF) is a common congenital heart malformation. Genetic variants in the CITED2 coding region are known to be significantly associated with cardiac malformation, but the role of variants in the CITED2 promoter region in the development of TOF remains unclear. In this study, we investigated CITED2 promoter variants in the DNA of 605 subjects, including 312 TOF patients and 293 unrelated healthy controls, by Sanger sequencing. We identified nine CITED2 gene promoter variants (including one novel heterozygous variant). Six were found only in patients with TOF and none in the control group. The transcriptional activity of the CITED2 gene promoter in mouse cardiomyocyte (HL-1) cells was significantly altered by the six variants (<i>p</i> < 0.05). The results of the electrophoretic mobility change assay and JASPAR database analysis showed that these variants generated or destroyed a series of possible transcription factor binding sites, resulting in changes in the CITED2 protein expression. We conclude that CITED2 promoter variants in TOF patients affect transcriptional activity and may be involved in the occurrence and progression of TOF. These findings may provide new insights into molecular pathogenesis and potential therapeutic insights in patients with TOF.https://www.mdpi.com/2218-273X/12/11/1644tetralogy of FallotCITED2geneticcardiac |
| spellingShingle | Zhuo Chen Huan-Xin Chen Hai-Tao Hou Xiu-Yun Yin Qin Yang Guo-Wei He Pathophysiological Role of Variants of the Promoter Region of CITED2 Gene in Sporadic Tetralogy of Fallot Patients with Cellular Function Verification Biomolecules tetralogy of Fallot CITED2 genetic cardiac |
| title | Pathophysiological Role of Variants of the Promoter Region of CITED2 Gene in Sporadic Tetralogy of Fallot Patients with Cellular Function Verification |
| title_full | Pathophysiological Role of Variants of the Promoter Region of CITED2 Gene in Sporadic Tetralogy of Fallot Patients with Cellular Function Verification |
| title_fullStr | Pathophysiological Role of Variants of the Promoter Region of CITED2 Gene in Sporadic Tetralogy of Fallot Patients with Cellular Function Verification |
| title_full_unstemmed | Pathophysiological Role of Variants of the Promoter Region of CITED2 Gene in Sporadic Tetralogy of Fallot Patients with Cellular Function Verification |
| title_short | Pathophysiological Role of Variants of the Promoter Region of CITED2 Gene in Sporadic Tetralogy of Fallot Patients with Cellular Function Verification |
| title_sort | pathophysiological role of variants of the promoter region of cited2 gene in sporadic tetralogy of fallot patients with cellular function verification |
| topic | tetralogy of Fallot CITED2 genetic cardiac |
| url | https://www.mdpi.com/2218-273X/12/11/1644 |
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