Genetic Variants of Gene Promoter Identified from Congenital Tetralogy of Fallot Patients Alter Cellular Function Forming Disease Basis.

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease in newborns. is a master transcription factor in second heart field development, whereas the roles of gene promoter variants in TOF patients have not been genetically investigated. Total DNA extraction from 601 human subjects, including 308 TOF patients and 293 healthy controls, and Sanger sequencing were performed. Four variants (including one novel heterozygous variant) within the gene promoter were only found in TOF patients. Functional analysis of DNA sequence variants was performed by using the dual-luciferase reporter assay and demonstrated that three of the four variants significantly decreased the transcriptional activity of gene promoter in HL-1 cells ( < 0.05). Further, the online JASPAR database and electrophoretic mobility shift assay showed that the three variants affected the binding of transcription factors and altered expression levels. In conclusion, the current study for the first time demonstrated that the variants identified from the gene promoter region are likely involved in the development of TOF by affecting the transcriptional activity and altering the expression level. Therefore, these findings may provide new insights into the molecular etiology and potential therapeutic strategy of TOF.