Novel and Functional DNA Sequence Variants within the GATA6 Gene Promoter in Ventricular Septal Defects

International Journal of Molecular Sciences

Chunyu Li³  Xianke Li⁴  Shuchao Pang²  Wei Chen¹  Xianyun Qin²  Wenhui Huang²  Changqing Zeng¹ 

[1] Laboratory of Genome Variation and Precision Biomedicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; E-Mail:;Shandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, Jining Medical University Affiliated Hospital, Jining Medical University, Jining 272029, China; E-Mails:;Division of Electrocardiogram, Jining Medical University Affiliated Hospital, Jining Medical University, Jining 272029, China; E-Mail:;Division of Anesthesia, Jining First People’s Hospital, Jining 272011, China; E-Mail:

关键词: congenital heart disease;    ventricular septal defect;    GATA6;    promoter;    DNA sequence variants;   

DOI  :  10.3390/ijms150712677

来源: mdpi

【 摘 要 】

Congenital heart disease (CHD) is the most common birth defect in humans. Genetic causes and underlying molecular mechanisms for isolated CHD remain largely unknown. Studies have demonstrated that GATA transcription factor 6 (GATA6) plays an essential role in the heart development. Mutations in GATA6 gene have been associated with diverse types of CHD. As GATA6 functions in a dosage-dependent manner, we speculated that changed GATA6 levels, resulting from DNA sequence variants (DSVs) within the gene regulatory regions, may mediate the CHD development. In the present study, GATA6 gene promoter was genetically and functionally analyzed in large groups of patients with ventricular septal defect (VSD) (n = 359) and ethnic-matched healthy controls (n = 365). In total, 11 DSVs, including four SNPs, were identified in VSD patients and controls. Two novel and heterozygous DSVs, g.22169190A>T and g.22169311C>G, were identified in two VSD patients, but in none of controls. In cultured cardiomyocytes, the activities of the GATA6 gene promoter were significantly reduced by the DSVs g.22169190A>T and g.22169311C>G. Therefore, our findings suggested that the DSVs within the GATA6 gene promoter identified in VSD patients may change GATA6 levels, contributing to the VSD development as a risk factor.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.