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.
BACKGROUND:Congenital heart disease (CHD) is the most common humanbirth 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 VSDpatients, 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 VSDpatients 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 VSDpatients 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.
Authors: Bohao Chen; Elena Yates; Yong Huang; Paul Kogut; Lan Ma; Jerrold R Turner; Yun Tao; Blanca Camoretti-Mercado; Deborah Lang; Eric C Svensson; Joe G N Garcia; Peter J Gruber; Edward E Morrisey; Julian Solway Journal: Am J Physiol Gastrointest Liver Physiol Date: 2009-09-24 Impact factor: 4.052
Authors: Maja Hempel; Teresa Casar Tena; Thilo Diehl; Martina S Burczyk; Tim M Strom; Christian Kubisch; Melanie Philipp; Davor Lessel Journal: Hum Genet Date: 2017-02-08 Impact factor: 4.132
Authors: Dhanya Ramachandran; Zhen Zeng; Adam E Locke; Jennifer G Mulle; Lora J H Bean; Tracie C Rosser; Kenneth J Dooley; Clifford L Cua; George T Capone; Roger H Reeves; Cheryl L Maslen; David J Cutler; Eleanor Feingold; Stephanie L Sherman; Michael E Zwick Journal: G3 (Bethesda) Date: 2015-07-20 Impact factor: 3.154