Novel and functional DNA sequence variants within the GATA5 gene promoter in ventricular septal defects

World J Pediatr. 2014 Nov;10(4):348-53. doi: 10.1007/s12519-014-0511-z. Epub 2014 Dec 17.


Background: Congenital heart disease (CHD) is the most common human birth defect. Genetic causes for CHD remain largely unknown. GATA transcription factor 5 (GATA 5) is an essential regulator for the heart development. Mutations in the GATA5 gene have been reported in patients with a variety of CHD. Since misregulation of gene expression have been associated with human diseases, we speculated that changed levels of cardiac transcription factors, GATA5, may mediate the development of CHD.

Methods: In this study, GATA5 gene promoter was genetically and functionally analyzed in large cohorts of patients with ventricular septal defect (VSD) (n=343) and ethnic-matched healthy controls (n=348).

Results: Two novel and heterozygous DNA sequence variants (DSVs), g.61051165A>G and g.61051463delC, were identified in three VSD patients, but not in the controls. In cultured cardiomyocytes, GATA5 gene promoter activities were significantly decreased by DSV g.61051165A>G and increased by DSV g.61051463delC. Moreover, fathers of the VSD patients carrying the same DSVs had reduced diastolic function of left ventricles. Three SNPs, g.61051279C>T (rs77067995), g.61051327A>C (rs145936691) and g.61051373G>A (rs80197101), and one novel heterozygous DSV, g.61051227C>T, were found in both VSD patients and controls with similar frequencies.

Conclusion: Our data suggested that the DSVs in the GATA5 gene promoter may increase the susceptibility to the development of VSD as a risk factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Child
  • Child, Preschool
  • China
  • Female
  • GATA5 Transcription Factor / genetics*
  • Genetic Predisposition to Disease
  • Heart Septal Defects, Ventricular / genetics*
  • Humans
  • Male
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Sequence Analysis, DNA


  • GATA5 Transcription Factor
  • GATA5 protein, human