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Genetic Variants of CITED2 Gene Promoter in Human Atrial Septal Defects: Case-Control Study and Cellular Functional Verification

Atrial septal defect (ASD) is one of the most common forms of congenital heart disease (CHD). Genetic variants in the coding region of the CITED2 gene are known to be significantly correlated with CHD, but the role of variants in the promoter region of CITED2 is unknown. We investigated variants in...

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Autores principales: Chen, Zhuo, Chen, Huan-Xin, Hou, Hai-Tao, Yin, Xiu-Yun, Yang, Qin, Han, Jun, He, Guo-Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604052/
https://www.ncbi.nlm.nih.gov/pubmed/36286273
http://dx.doi.org/10.3390/jcdd9100321
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author Chen, Zhuo
Chen, Huan-Xin
Hou, Hai-Tao
Yin, Xiu-Yun
Yang, Qin
Han, Jun
He, Guo-Wei
author_facet Chen, Zhuo
Chen, Huan-Xin
Hou, Hai-Tao
Yin, Xiu-Yun
Yang, Qin
Han, Jun
He, Guo-Wei
author_sort Chen, Zhuo
collection PubMed
description Atrial septal defect (ASD) is one of the most common forms of congenital heart disease (CHD). Genetic variants in the coding region of the CITED2 gene are known to be significantly correlated with CHD, but the role of variants in the promoter region of CITED2 is unknown. We investigated variants in the promoter of the CITED2 gene in 625 subjects (332 ASD and 293 healthy controls) through Sanger sequencing. Four variants in the CITED2 gene promoter were found only in eight ASD patients with zero occurrence in the control subjects (one case of g.4078A>C(rs1165649373), one case of g.4240C>A(rs1235857801), four cases of g.4935C>T(rs111470468), two cases of g.5027C>T(rs112831934)). Cellular functional analysis showed that these four variants significantly changed the transcriptional activity of the CITED2 gene promoter in HEK-293 and HL-1 cells. Electrophoretic mobility change assay results and JASPAR database analysis demonstrated that these variants created or destroyed a series of possible transcription factor binding sites, resulting in changes in the expression of CITED2 protein. We conclude that the variants of CITED2 promoter in ASD patients affect the transcriptional activity and are likely involved in the occurrence and development of ASD. These findings provide new perspectives on the pathogenesis and potential therapeutic insights of ASD.
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spelling pubmed-96040522022-10-27 Genetic Variants of CITED2 Gene Promoter in Human Atrial Septal Defects: Case-Control Study and Cellular Functional Verification Chen, Zhuo Chen, Huan-Xin Hou, Hai-Tao Yin, Xiu-Yun Yang, Qin Han, Jun He, Guo-Wei J Cardiovasc Dev Dis Article Atrial septal defect (ASD) is one of the most common forms of congenital heart disease (CHD). Genetic variants in the coding region of the CITED2 gene are known to be significantly correlated with CHD, but the role of variants in the promoter region of CITED2 is unknown. We investigated variants in the promoter of the CITED2 gene in 625 subjects (332 ASD and 293 healthy controls) through Sanger sequencing. Four variants in the CITED2 gene promoter were found only in eight ASD patients with zero occurrence in the control subjects (one case of g.4078A>C(rs1165649373), one case of g.4240C>A(rs1235857801), four cases of g.4935C>T(rs111470468), two cases of g.5027C>T(rs112831934)). Cellular functional analysis showed that these four variants significantly changed the transcriptional activity of the CITED2 gene promoter in HEK-293 and HL-1 cells. Electrophoretic mobility change assay results and JASPAR database analysis demonstrated that these variants created or destroyed a series of possible transcription factor binding sites, resulting in changes in the expression of CITED2 protein. We conclude that the variants of CITED2 promoter in ASD patients affect the transcriptional activity and are likely involved in the occurrence and development of ASD. These findings provide new perspectives on the pathogenesis and potential therapeutic insights of ASD. MDPI 2022-09-23 /pmc/articles/PMC9604052/ /pubmed/36286273 http://dx.doi.org/10.3390/jcdd9100321 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chen, Zhuo
Chen, Huan-Xin
Hou, Hai-Tao
Yin, Xiu-Yun
Yang, Qin
Han, Jun
He, Guo-Wei
Genetic Variants of CITED2 Gene Promoter in Human Atrial Septal Defects: Case-Control Study and Cellular Functional Verification
title Genetic Variants of CITED2 Gene Promoter in Human Atrial Septal Defects: Case-Control Study and Cellular Functional Verification
title_full Genetic Variants of CITED2 Gene Promoter in Human Atrial Septal Defects: Case-Control Study and Cellular Functional Verification
title_fullStr Genetic Variants of CITED2 Gene Promoter in Human Atrial Septal Defects: Case-Control Study and Cellular Functional Verification
title_full_unstemmed Genetic Variants of CITED2 Gene Promoter in Human Atrial Septal Defects: Case-Control Study and Cellular Functional Verification
title_short Genetic Variants of CITED2 Gene Promoter in Human Atrial Septal Defects: Case-Control Study and Cellular Functional Verification
title_sort genetic variants of cited2 gene promoter in human atrial septal defects: case-control study and cellular functional verification
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604052/
https://www.ncbi.nlm.nih.gov/pubmed/36286273
http://dx.doi.org/10.3390/jcdd9100321
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