title: Novel and functional DNA sequence variants within the GATA5 gene promoter in ventricular septal defects.
abstract: 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.
  
  
  CONCLUSIONS
  Our data suggested that the DSVs in the GATA5 gene promoter may increase the susceptibility to the development of VSD as a risk factor.
authors.affiliation: Shandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, China.
authors.forename: Ji-Ping
authors.initials: JP
authors.lastname: Shan
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Wang
authors.forename: Yuan-Gang
authors.initials: YG
authors.lastname: Qiao
authors.forename: Hong-Xin
authors.initials: HX
authors.lastname: Wan Yan
authors.forename: Wen-Hui
authors.initials: WH
authors.lastname: Huang
authors.forename: Shu-Chao
authors.initials: SC
authors.lastname: Pang
authors.forename: Bo
authors.initials: B
authors.lastname: Yan
mesh_terms: D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002681:China; D005260:Female; D050992:GATA5 Transcription Factor / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006345:Heart Septal Defects, Ventricular / Q000235:genetics*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D017422:Sequence Analysis, DNA
chemical_list: D050992:GATA5 Transcription Factor; C494755:GATA5 protein, human