[Association of ventricular septal defect with rare variations of the gene].

OBJECTIVES

To study the association of ventricular septal defect (VSD) with rare variations in the promoter region of gene, as well as related molecular mechanisms.

METHODS

Blood samples were collected from 349 children with VSD and 345 healthy controls. The target fragments were amplified by polymerase chain reaction and sequenced to identify the rare variation sites in the promoter region of the gene. Dual-luciferase reporter assay was used to perform a functional analysis of the variation sites. Electrophoretic mobility shift assay (EMSA) was used to investigate related molecular mechanisms. TRANSFAC and JASPAR databases were used to predict transcription factors.

RESULTS

Sequencing revealed that three variation sites (g.173530852A>G, g.173531173A>G, and g.173531213C>G) were only observed in the promoter region of the gene in 10 children with VSD, among whom 4 children had only one variation site. The dual-luciferase reporter assay revealed that g.173531213C>G reduced the transcriptional activity of the gene promoter. EMSA and transcription factor prediction revealed that g.173531213C>G created a binding site for transcription factor.

CONCLUSIONS

The rare variation, g.173531213C>G, in the promoter region of the gene participates in the development and progression of VSD possibly by affecting the binding of transcription factors.