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Genetic analysis of the CITED2 gene promoter in isolated and sporadic congenital ventricular septal defects

Ventricular septal defect (VSD) is the most common congenital heart defect. Previous studies have reported genetic variations in the encoding region of CITED2 highly associated with cardiac malformation but the role of CITED2 gene promoter variations in VSD patients has not yet been explored. We inv...

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Autores principales: Zheng, Si‐Qiang, Chen, Huan‐Xin, Liu, Xiao‐Cheng, Yang, Qin, He, Guo‐Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882930/
https://www.ncbi.nlm.nih.gov/pubmed/33439552
http://dx.doi.org/10.1111/jcmm.16218
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author Zheng, Si‐Qiang
Chen, Huan‐Xin
Liu, Xiao‐Cheng
Yang, Qin
He, Guo‐Wei
author_facet Zheng, Si‐Qiang
Chen, Huan‐Xin
Liu, Xiao‐Cheng
Yang, Qin
He, Guo‐Wei
author_sort Zheng, Si‐Qiang
collection PubMed
description Ventricular septal defect (VSD) is the most common congenital heart defect. Previous studies have reported genetic variations in the encoding region of CITED2 highly associated with cardiac malformation but the role of CITED2 gene promoter variations in VSD patients has not yet been explored. We investigated the variation of CITED2 gene promoter and its impacts on gene promoter activity in the DNA of paediatric VSD patients. A total of seven variations were identified by Sanger sequencing in the CITED2 gene promoter region in 400 subjects, including 200 isolated and sporadic VSD patients and 200 healthy controls. Using dual‐luciferase reporter assay, we found four of the 7 variations identified significantly decreased the transcriptional activity of the CITED2 gene promoter in HEK‐293 cells (P < .05). Further, a bioinformatic analysis with the JASPAR databases was performed and a cluster of putative binding sites for transcription factors was created or disrupted by these variations, leading to low expression of CITED2 protein and development of VSD. Our study for the first time demonstrates genetic variations in the CITED2 gene promoter in the Han Chinese population and the role of these variations in the development of VSD, providing new insights into the aetiology of CHD.
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spelling pubmed-78829302021-02-19 Genetic analysis of the CITED2 gene promoter in isolated and sporadic congenital ventricular septal defects Zheng, Si‐Qiang Chen, Huan‐Xin Liu, Xiao‐Cheng Yang, Qin He, Guo‐Wei J Cell Mol Med Original Articles Ventricular septal defect (VSD) is the most common congenital heart defect. Previous studies have reported genetic variations in the encoding region of CITED2 highly associated with cardiac malformation but the role of CITED2 gene promoter variations in VSD patients has not yet been explored. We investigated the variation of CITED2 gene promoter and its impacts on gene promoter activity in the DNA of paediatric VSD patients. A total of seven variations were identified by Sanger sequencing in the CITED2 gene promoter region in 400 subjects, including 200 isolated and sporadic VSD patients and 200 healthy controls. Using dual‐luciferase reporter assay, we found four of the 7 variations identified significantly decreased the transcriptional activity of the CITED2 gene promoter in HEK‐293 cells (P < .05). Further, a bioinformatic analysis with the JASPAR databases was performed and a cluster of putative binding sites for transcription factors was created or disrupted by these variations, leading to low expression of CITED2 protein and development of VSD. Our study for the first time demonstrates genetic variations in the CITED2 gene promoter in the Han Chinese population and the role of these variations in the development of VSD, providing new insights into the aetiology of CHD. John Wiley and Sons Inc. 2021-01-13 2021-02 /pmc/articles/PMC7882930/ /pubmed/33439552 http://dx.doi.org/10.1111/jcmm.16218 Text en © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Zheng, Si‐Qiang
Chen, Huan‐Xin
Liu, Xiao‐Cheng
Yang, Qin
He, Guo‐Wei
Genetic analysis of the CITED2 gene promoter in isolated and sporadic congenital ventricular septal defects
title Genetic analysis of the CITED2 gene promoter in isolated and sporadic congenital ventricular septal defects
title_full Genetic analysis of the CITED2 gene promoter in isolated and sporadic congenital ventricular septal defects
title_fullStr Genetic analysis of the CITED2 gene promoter in isolated and sporadic congenital ventricular septal defects
title_full_unstemmed Genetic analysis of the CITED2 gene promoter in isolated and sporadic congenital ventricular septal defects
title_short Genetic analysis of the CITED2 gene promoter in isolated and sporadic congenital ventricular septal defects
title_sort genetic analysis of the cited2 gene promoter in isolated and sporadic congenital ventricular septal defects
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882930/
https://www.ncbi.nlm.nih.gov/pubmed/33439552
http://dx.doi.org/10.1111/jcmm.16218
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