Mutations of NKX2.5 and GATA4 genes in the development of congenital heart disease

Gene. 2016 Aug 15;588(1):86-94. doi: 10.1016/j.gene.2016.04.061. Epub 2016 May 3.


Objective: To investigate the mutations of NKX2.5 and GATA4 genes in the development of CHD in Chinese population.

Methods: Between December 2010 and December 2014, 185 cases of CHD patients and 210 cases of healthy people were enrolled. NKX2.5 and GATA4 gene mutations and gene expression were detected via DNA sequencing and real-time PCR (RT-PCR), respectively. BMSCs were transfected with pCMV-HA-NKX2.5 and pCMV-Myc-GATA4 plasmids. Cardiac troponin T (cTnT) and connexin 43 (Cx43) and β-myosin heavy chain (β-MHC) and myosin light chain-2 (MLC-2) expressions were detected. Co-immunoprecipitation assay was used to detect the interaction of NKX2.5 and GATA4 and luciferase to detect their effect on B-type natriuretic peptide (BNP) gene promoter.

Results: NKX2.5 and GATA4 gene mutations were found in the CHD group, but not in the normal control group, and NKX2.5 and GATA4 gene expressions were significantly lower in the case group compared with the control group (both P<0.05). Compared to the control and empty vector groups, cTnT and Cx43 expressions were significantly higher in the pCMV-HA-NKX2.5 and pCMV-Myc-GATA4 plasmid groups; β-MHC at 1-4weeks and MLC-2 at 2-4weeks were higher in the pCMV-HA-NKX2.5 plasmid group; and β-MHC at 2-3weeks and MLC-2 at 3-4weeks were higher in the pCMV-Myc-GATA4 plasmid group (all P<0.05). NKX2.5 and GATA4 interacted in the BMSCs and co-transfected pCMV-Myc-GATA4 and pCMV-HA-NKX2.5 significantly enhanced the fluorescence intensity of BNP.

Conclusion: NKX2.5 and GATA4 gene mutations might participate in the development of CHD and can promote BMSCs differentiate into cardiomyocytes.

Keywords: Congenital heart disease; GATA4; Gene mutation; NKX2.5; Transcription factors.

MeSH terms

  • Animals
  • Asian Continental Ancestry Group / genetics
  • Case-Control Studies
  • Cell Differentiation
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Female
  • GATA4 Transcription Factor / genetics*
  • Genetic Predisposition to Disease*
  • Heart Defects, Congenital / genetics*
  • Homeobox Protein Nkx-2.5 / genetics*
  • Humans
  • Male
  • Mesenchymal Stem Cells / pathology
  • Myocytes, Cardiac
  • Pedigree
  • Rats
  • Rats, Sprague-Dawley


  • GATA4 Transcription Factor
  • GATA4 protein, human
  • Homeobox Protein Nkx-2.5
  • NKX2-5 protein, human