Premium
Genetic Analysis of the CITED2 Gene Promoter in Isolated and Sporadic Congenital Ventricular Septal Defects
Author(s) -
Zheng SiQiang,
Chen HuanXin,
Liu XiaoCheng,
Yang Qin,
He GuoWei
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.02655
Subject(s) - promoter , gene , gata4 , luciferase , reporter gene , sanger sequencing , biology , genetics , gene expression , microbiology and biotechnology , transcription factor , dna sequencing , transfection
Objectives 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. Methods In 400 subjects (200 isolated and sporadic VSD patients: 200 healthy controls), We investigated the variation of CITED2 gene promoter and performed cellular functional experiments by using the dual‐luciferase reporter assay to verify the impact on gene expression. Results A total of 7 variations were identified by Sanger sequencing in the CITED2 gene promoter region. 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 < 0.05). 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. Conclusions 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 etiology of CHD.